HiCcompare provides functions for joint normalization and difference detection in multiple Hi-C datasets. HiCcompare operates on processed Hi-C data in the form of chromosome-specific chromatin interaction matrices. It accepts three-column tab-separated text files storing chromatin interaction matrices in a sparse matrix format which are available from several sources. HiCcompare is designed to give the user the ability to perform a comparative analysis on the 3-Dimensional structure of the genomes of cells in different biological states.HiCcompare differs from other packages that attempt to compare Hi-C data in that it works on processed data in chromatin interaction matrix format instead of pre-processed sequencing data. In addition, HiCcompare provides a non-parametric method for the joint normalization and removal of biases between two Hi-C datasets for the purpose of comparative analysis. HiCcompare also provides a simple yet robust method for detecting differences between Hi-C datasets.