Abstract: Objective: To investigate the role and significance of hMSH2 and hMLH1 protein expression in gastric carcinogenesis. Methods: We collected 172 samples of gastric carcinoma (GCs),151 samples of mucosa surrounding gastric cancer (SMs) and 34 samples of gastric mucosa from non-cancer patients (NGMs). Immunohistochemistry was employed to detect hMSH2 and hMLH1 protein expression, and Chi- square test and Spearman correlation analysis were used to analyze the results.Results: In GCs, SMs and NGMs, the expression rates of hMSH2 protein were 69.8% (120/172), 49.7% (75/151) and 32.4% (11/34), respectively (GC vs. SM and NGM, P=0.000; SM vs. NGM, P=0.067); those of hMLH1 protein were 73.3% (126/172), 57.6% (87/151) and 41.2% (14/34), respectively (GC vs. SM and NGM, P=0.000; SM vs. NGM, P=0.082). The rates of hMSH2 and hMLH1 protein expression were not significantly correlated with the age or gender of the GC patients or with the differentiation of GC. In GCs, SMs and NGMs, hMSH2 protein positive expression rates were 70.0% (84/120), 58.7% (44/75) and 36.4% (4/11), respectively, in the nucleus, and 30.0% (36/120), 41.3% (31/75), 63.6% (7/11), respectively, in the cytoplasm. No significant difference was found for the location of hMLH1 protein expression. Conclusion: Detection of hMSH2 and hMLH1 proteins in gastric mucosa and analysis of the location of their intracellular expression may be helpful for early diagnosis of gastric carcinoma.