Mismatch repair (MMR) system is one form of DNA repair mechanisms, which plays an important role in rectifying the mismatch of base pairs, reducing gene mutations and keeping genome stability. Abnormal expression of MMR regulated by miRNA is closely related to the development of colon cancer. Functional defects of MMR (dMMR) with particular clinical characteristics can be used as a potential prognostic and predictive biomarker. This article reviews the relation between MMR system, miRNA and colon cancer.