In this paper, we present and study the \emph{Hamming distance oracle problem}. In this problem, the task is to preprocess two strings S and T of lengths n and m, respectively, to obtain a data-structure that is able to answer queries regarding the Hamming distance between a substring of S and a substring of T. For a constant size alphabet strings, we show that for every x≤nm there is a data structure with O~(nm/x) preprocess time and O(x) query time. We also provide a combinatorial conditional lower bound, showing that for every ε>0 and x≤nm there is no data structure with query time O(x) and preprocess time O((xnm)1−ε) unless combinatorial fast matrix multiplication is possible. For strings over general alphabet, we present a data structure with O~(nm/x) preprocess time and O(x) query time for every x≤nm.