Abstract: Objective: To study methylation of E-CD and hMLH1 in gastric cancer, precancerous lesions and normal gastric tissue to discover the molecular changes in gastric carcinogenesis. Methods:MSP was used to detect methylation of E-CD and hMLH1. Immunohistochemistry was adopted to detectthe expression of E-CD and hMLH1 protein. Results: The positive rate of E-CD methylation in gastriccancer group was higher than that in precancerous lesions and normal group, which was correlated with differentiation, invasion depth, lymph node metastasis and TNM stage . The positive rate of hMLH1 methylation in gastric cancer group was higher than that in the precancerous lesions and the normalgroups. The positive rate of MSI in gastric cancer group is higher compared to the precancerous lesionsand the normal groups. Conclusions: MSI and methylation of E-CD and hMLH1 can be good markersfor predicting carcinogenesis and prognosis of gastric cancer.