Abstract: Objective : To study the protein expression of mismatch repair (MMR) gene hMSH2 in the development of oral squamous cell carcinoma (OSCC). Methods : A total of 33 samples, including OSCC and corresponding tumor-adjacent and normal tissues, were investigated for the changes on the amount and location of hMSH2 protein in the development of OSCC by using Western Blot and im-munohistochemical test. Results : Significantly higher expression of hMSH2 was detected in the samples of carcinoma, but no such promotion was found in the tumor-adjacent and normal tissues. The positive expression of hMSH2 protein in nuclei was only observed in the base cells of the normal tissue, while it was correlated to the development of dysplasia in the tumor-adjacent tissues. In the cancer tissues all the epithelial cells were detected to be positive immunoreactivily in nuclei. The cytoplasms of all the cells were shown negative immunoreactivity. Conclusion : There may be protective epigenetic inheri-tance regulation of hMSH2 in the carcinogenesis of OSCC.