Abstract: Objective：To investigate the significance and relation of transforming growth factor-β type Ⅱ receptor gene and hMLH1 gene in carcinogenesis of esophageal mucosa epithelium. Methods：The expression of transforming growth factor-β type Ⅱ receptor gene and hMLH1 gene in normal esophageal mucosa epithelium and variant lesions were detected by immunohistochemistry,and their correlation with clinicopathological parameters were analysed as well. Results：The positive expression rate (14.29%) of hMLH1 in esophageal squamous cell carcinoma is significantly lower than that in normal esophageal mucosa epithelium (95.00%)，atypical hyperplasia（71.43%）, carcinoma in situ （68.00%）（P<0.05）;which showed statistical significance. The positive expression rate (9.52%) of TGFβRⅡ in esophageal squamous cell carcinoma is significantly lower than that in normal esophageal mucosa epithelium(85.00%)，atypical hyperplasia （61.90%）, carcinoma in situ （64.00%）（P<0.05）;which showed statistical significance. The positive expression of hMLH1 and Transforming growth factor-β type Ⅱ receptor had close correlation with the differentiation of esophageal carcinoma;the expression of hMLH1 and TGFβRⅡ in esophageal squamous cell carcinoma had correlation. Conclusion ：The abnormal expression of hMLH1 protein may be related with the carcinogensis of the esophageal squamous cell. Transforming growth factor-β type Ⅱ receptor may be the target gene of hMLH1.