Abstract: Objective: To detect the CDH1 gene methylation and mutation in exon at different pathological stages of tongue mucosa carcinogenesis. Methods: Seventy-five SD rats were administered by 0.004% 4-nitroquinoline-1-oxide (4NQO) in drinking water, and 15 SD rats were kept in the same conditions without 4NQO as negative control group. After 10, 14, 18, 22 and 24 weeks, the rats were euthanatized, and the tumorsin the tongue mucosa were collected for histological examination and DNA extraction. Then, methylation specific polymerase chain reaction (MS-PCR) was performed to detect the levels of CDH1 promoter methylation, and PCR amplification of CDH1 exons 1-16 was performed to detect CDH1 exons mutations in the various stages of tongue squamous cell carcinoma (TSCC). Results: There were no CDH1 promoter methylation specific products detected in different stages of SD rats TSCC. In sequenced exons 1-16 of all samples, only exon 13 mutation was detected at the site of mRNA 2106 (G→T). Conclusion: CDH1 mutations in exons may be associated with the development of SD rats TSCC which induced by 4NQO, but CDH1 promoter methylation was not.