Objective To investigate the expressions of cytokeratin/keratin 4 in the buccal tissue of oral submucous fibrosis at the early,middle and advanced stages,explore which role keratin4 (K4) plays in the process and development of oral submucous fibrosis (OSF),and provide evidence for K4 being a promising biomarker to evaluate the development and prognosis of OSF.Methods Ten cases of normal tissues,and 10 cases of OSF tissues with typical early,middle and advanced stages,were selected,respectively.Detect the expression of K4 in the tissue mentioned above through immunohistochemistry and Westem blot.The data was analyzed by statistical means.Results The results of immunohistochemistry showed that K4 was mainly located in cytoplasm,and positive cells with brownish yellow granules were seen in whole epithelial layer of the normal mucosa.The expression of K4 was lower at all stages of OSF than that at the normal tissue with statistical significance (P ＜0.05).With the aggravation of OSF,the expression of K4 was decreased,difference between early and advanced stage was found to be statistically significant.The results of Western blot also showed that the expression of K4 was lower than that of early,middle and advanced stages of OSF (P ＜ 0.05).With the aggravation of OSF,the expression of K4 was decreased,but the differences between them had no significance (P ＞ 0.05).Conclusions The expression of K4 in OSF tissue of early,middle and advanced stages were decreased compared to normal tissue,respectively.It suggests that K4 might play and important role in the initiation and development of OSF.