p16(CDKN2A) is one of the most important tumor-suppressor genes and has been investigated widely in recent years for its role in oral carcinogenesis, but few have explored the relationship between its RNA and protein, especially in precancerous tissues. The aim of this study was to explore the relationship of mRNA and protein level of p16(CDKN2A) in rat tongue carcinogenesis process induced by 4-nitroquinoline-1-oxide. By the use of semi-quantitative RT-PCR, immunohistochemistry (IHC) and Western Blot, histologically normal, premalignant and invasive squamous cell carcinoma samples from the animal model were explored respectively. The results showed the levels of mRNA of p16(CDKN2A) did not significantly change during the carcinogenesis process when compared with controls. However, detectable level of P16 protein expression was lost in both the dysplasia and carcinoma groups. We could conclude that p16(CDKN2A) in 4NQO-induced rat tongue carcinogenesis might be inactivated predominantly by posttranscriptional regulation.