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OBJECTIVE To investigate the effect of Helicobacter pylori (H pylori) infection on expression of hMSH2 and P53 and its possible carcinogenic mechanism.METHODS H pylori infection was detected using a rapid urease test and haematoxylin and eosin (H&E) staining. The hMSH2 and P53 proteins in gastric cancer (GC) tissue, its adjacent mucosa, gastritic mucosa and normal gastric mucosa were detected by the immunohistochemical SP method.RESULTS (1) The positive rate of hMSH2 expression in GC tissue(62.7%)was higher than those in non-cancer tissues (P＜0.001); the positive rate of hMSH2 expression in poorly differentiated adenocarcinoma (76.4%) was higher than that in other carcinomas (P＜0.05). The positive rate of P53 expression in GC tissue (51.9%) was higher than that in noncancer tissues (P＜0.001); the positive rate of P53 expression in well-differentiated adenocarcinoma (32.6 %) was lower than that in other carcinomas (P＜0.01). (2) The positive rate of hMSH2 expression in GC tissue with H pylori infection was lower than that without the infection (52.8% vs.74.5%; P＜0.05). The positive rate of P53 expression in GC tissue with H pylori infection was higher than that without the infection (61.4% vs.40.6%; P＜0.05).(3) The expression of hMSH2 and P53 in GC tissue correlated positively (r=0.457, P＜0.01).CONCLUSION High expression of hMSH2 and P53 as well as their interaction may be involved in gastric carcinogenesis; H pylori infection affecting expression of hMSH2 and P53 may be one of its carcinogenic mechanisms.