A skeptical hypothesis is centered around an assumption that we will never know anything that we experience whether it is a truth or falsehood since there is always a possibility that everything we experience, encounter and believe it turned out to be a deception. This deception is manufactured so that one experiences of the world would be as genuine as if one had not been deceived.
The problem with a skeptical hypothesis is “we seem unable to know they are false” (Pritchard, 170). This raises an alarm since we will never know how to differentiate our real experience with the world and with the illusory one. Furthermore, a skeptical hypothesis is used in the construction of the skeptical argument. Sceptical hypothesis plays a role as a premise that entails the validity of the conclusion. And because of the contradictory nature of the skeptical hypothesis, the skeptical argument thus becomes a paradox. To understand it better, one can give an example. One of the famous examples about skepticism is brain-in-a-vat argument.
Imagine the possibility that at this very moment you are actually a brain hooked up to a sophisticated computer program that can perfectly simulate experiences of the outside world. Here is the skeptical argument. If you cannot now be sure that you are not a brain in a vat, then you cannot rule out the possibility that all of your beliefs about the external world are false. Or, to put it in terms of knowledge claims, we can construct the following skeptical argument. Let “P” stand for any belief or claim about the external world, say, that snow is white.
§ If I know that P, then I know that I am not a brain in a vat
§ I do not know that I am not a brain in a vat
§ Thus, I do not know that P.
The Brain in a Vat Argument is usually taken to be a modern version of René Descartes’ argument (in the Meditations on First Philosophy) that centers on the possibility of an evil demon who systematically deceives us. The hypothesis has been the premise behind the movie The Matrix, in which the entire human race has been placed into giant vats and fed a virtual reality at the hands of malignant artificial intelligence (our own creations, of course). 
Another more sophisticated example is given below.
Physics is one of a most relevant subject to describe nature. the triumphant of physics cannot be separated with the use of mathematics as the fundamental tools in developing and explaining physics. It is widely used that no one cannot deny the importance of Mathematics in Physics. Both have a mutual relationship that cannot be separated. More sophisticated development in Physics can only happen if Mathematics develops into a new area/new realm and development in Mathematics can happen if new Physics is discovered through experiment and observation. All basics technologies nowadays once at one time just a series of logical argument using mathematics formula in hand of physicists.
Now, if all events in nature can be explained through Physics and Mathematics by extension, how can we be sure that Mathematics/Physics (that we have) is true (globally/objectively)?
To answer this question, we need to go deep in the heart of Mathematics. Modern Mathematics is built by series of postulates, theorems, and axioms. Whereas we know the object of mathematics such as numbers, sets, maps and all the operations don’t exist physically in the material world. They are built by series of arguments that inherently consistent with the law of logic. Loosely speaking, Mathematics is built on basic agreements/assumptions/postulates that can be added or subtracted and believed to be true (without doing this, Mathematics cannot be explained). Mathematics would be totally different if we start from the different set of postulates and will also impact the Physics that we believe in, while nature always has been, and will be in their state. The apple will always fall to the ground (on Earth) regardless the law of gravity is true or not.
The problem arises when we realize that there is no way to verify that our description of nature through the current Physics supported by Mathematics is a justified true belief or not. Let me illustrate. The only known method by Physicist to justify their beliefs is through a method called an experiment. But since the experiment itself based its fundamental principles in measurement that is built by using Mathematics and must obey set of rules that are called the law of Physics, implies that the tool of justification itself will be a-kind-a-circular reasoning and would be vastly different if we had different sets of basic postulates in Mathematics.
One can think: if Physics and its experiments can change when “Mathematics changes” while the world we experience always the same, then is our explanation of nature in Physics true or not?
This becomes a skeptical hypothesis. Because whatever explanation we come up in Physics about how Nature behaves, we can always come up with entirely different Physics to explain it and verify it through experiment (because the nature of the experiment is artificially built through that Physics and Mathematics). Physicists can never be sure that mathematical/physical description of laws of nature is true or false.
Now we can apply the skeptical argument:
Premise 1: Physicists are unable to know the denials that Physics (that they have) is not the true representation of nature. (by true we mean one and only way of representing natural processes in mathematical language and formulation)
Premise 2: If Physicists are unable to know the denials that Physics that they have is not the true representation of nature then they are unable to know anything about nature at all
Conclusion: Physicists are unable to know anything about nature at all.
If one wonders what the sceptical arguments in general are made, one can refer to (Pritchard, 170).
This line of thought using the very logic that entails the notation of knowledge itself giving the sceptical conclusion shows the paradox properties of sceptical argument. And paradox is largely produced by sceptical hypothesis as its premise.
Furthermore, the strong claim of premise 2 is the characteristic of so called radical sceptical arguments. To feel its “radical sense” one can apply the closure principle.
Closure Principle: If Physicists know nature behaves as their formulation of Physics and is verified by experiment, then their formulation of Physics must be right. If their formulation is right, then it cannot be false.
But because of the Physicists cannot rule out the possibility of their physics is not the only physics and experiments are loosely based on their interest by manipulating mathematics, they are unable to claim that nature behaves like their physics, hence they are unable to know anything about nature at all. This is the conclusion above, again.
 Pritchard, D. (2014). What is this thing called knowledge?. 3rd ed. Oxon: Routledge, p.23, p.55, pp. 105-106, p.170, pp.183-184
 http://www.iep.utm.edu/brainvat/ (partially taken)