Let S be an arbitrary subset of R n where R is a domain with the field of fractions K. Denote the ring of polynomials in n variables over K by K[x]. The ring of integer-valued polynomials over S, denoted by Int(S, R), is defined as the set of the polynomials of K[x], which maps S to R. In this article, we study the irreducibility of the polynomials of Int(S, R) for the first time in the case when R is a Unique Factorization Domain. We also show that our results remain valid when R is a Dedekind domain or sometimes any domain.