Objective: To investigate the relationship between the expression of tumor suppressor gene PTEN and p16 protein and the biologcal behaviors of cholangiocarcinomas.Methods: The expression of PTEN and p16 protein in 43 of cholangiocarcinoma tissues and 10 chronic cholangitis tissues were investigated by immunohistochemical technique.The relationship between expression of PTEN and p16 protein and the clinicopathological parameters of cholangiocarcinoma was analyzed. Results :The positive expression rate of PTEN and p16 protein in cholangiocarcinoma was 39.5％ and 44.2％,respectively.The expression of PTEN and p16 protein were positively relatad with the TNM staging,differentiation degree and metastasis of cholangiocarcinoma (P<0.05).Moreover,there was a positive correlation between the PTEN and p16 protein expression in cholangiocarcinoma(r=0.49,P<0.005).Conclusions: Expression of tumor suppressor gene PTEN and p16 could be helpful in predicting the biological behavior and prognosis of cholangiocarcinoma.