Objective To study the expression and significance of apoptosis-related genes caspase-3, caspase-9, Bax and Bcl-2 in oral normal mucosa, oral simple hyperplasia, oral epithelial dysplasia and oral squamous cell carcinomas (OSCC) in Chinese hamsters. Methods The expressions of mRNA and protein of caspase-3, caspase-9, Bax and Bcl-2 in the oral normal mucosa, oral simple hyperplasia, oral epithelial dysplasia and OSCC tissues in Chinese hamsters were examined by immunohistochemistry and RT-PCR. Results During the process of oral carcinogenesis, the expression of Bcl-2 protein was significantly higher in OSCC than in oral normal mucosa, oral simple hyperplasia, and oral epithelial dysplasia (P<0.05). In dysplastic epithelia, the protein expressions of caspase-3, caspase-9 and Bax were more than that of normal epithelia, and along with the increased dysplasis, the expression level was decreased. Further analysis showed that expression of Bcl-2 was negatively related with the expressions of Bax, caspase-3 and caspase-9 (P<0.05). The result of RT-PCR showed that Bcl-2 was significantly increased in OSCC compared with normal mucosa, while the expressions of caspase-3, caspase-9 and Bax were decreased (P<0.05). Conclusions In the Chinese hamster squamous carcinoma, the expressions of caspase-3, caspase-9 and Bax are reduced and the Bcl-2 expression are increased, indicating that the expressions of caspase-3, caspase-9, Bax and Bcl-2 are closely related with the occurrence and development of oral squamous cell cancinoma. This study can offer some clues for gene therapy of OSCC, or can provide a reference for evaluating the biological characteristics and prognosis of OSCC.