DNA mismatch repair (MMR) gene plays vital role in repairing the mismatch of DNA bases and keeping the faithful duplication of the genetic material, so as to ensure the fidelity of DNA replication. Defects of MMR genes leads to the accumulation of numerous mutations across the genome, and then creates a molecular phenotype known as microsatellite instability (MSI). In recent years, there are many researches about the relationship of MMR with gastric cancer. Much evidence shows that the prognosis and chemotherapy sensitivity of gastric cancer are quite different from the tumors with MSI and those with microsatellite stability (MSS). In this review, we elucidated the role of MMR in the pathogenesis and its significance in the prognosis of gastric cancer.