Abstract: Objective： To establish a more realistic animal model for oral carcinogenesis and study the expression changes of double ubiquitin FAT10 in the process of development in this model. Methods：The experimental group SD rats were fed with 40 μg/mL concentration of 4-nitroquinoline1-oxide (4-NQO) dissolved in drinking water. The lesion tissue of rat tongue was collected in 8, 16 and 24 weeks respectively, and detected by histology. The rats in control group were fed with normal drinking water for 24 weeks. Immunohistochemistry was used to detect the expression of FAT10 and p53 in different tissues of the tongue mucosa. Results：Being stimulated with 4-NQO at different time, the tongue mucosa of rats developed dysplasia of varying degrees and squamous cell carcinoma. The expression of FAT10 increased gradually from normal mucosa to atypical hyperplasia and squamous cell carcinoma. The espression of p53 was positive in normal mucosa, and increased in atypical hyperplasia, but was decreased in cancer tissues. Conclusions：FAT10 might be an oncogene in the development of tongue cancer.