Abstract: Objective: To study the relationship between the extrahepatic bile duct carcinoma and the CD81, a cell receptor for hepatitis C virus. Methods: Nested reverse transcriptase-polymerase chain reaction (nested RT-PCR) and immunohistochemistry assays were used to detect the expression of HCV RNA, CD81 mRNA, NS5 and CD81 protein in tissues of 62 patients with extrahepatic bile duct carcinoma. The control group included 30 patients with benign lesion of hepatobiliary ducts. Results:The positive expression rate of HCV RNA and CD81 mRNA in tissues of extrahepatic bile duct carcinoma was 58.1% and 6.7% respectively. Compared to the group of benign hepatobiliary lesions, there was a statistically significant difference(P<0.01). The expression rate of CD81 mRNA in tissues of extrahepatic bile duct carcinoma with HCV RNA(+) and HCV RNA(-) was 55.6% and 96.2%, respectively and there was a statistical difference between the two(P<0.001). The results of immunohistochemitry assays were similar. The loss of CD81 in 36 cases of extrahepatic bile duct carcinoma with HCV RNA(+) was prominent and associated with the differentiation of extrahepatic bile duct carcinoma (X²=14.103, P<0.01). The difference of CD81 loss between high differentiated cases (Ⅰgrade) and poorly differentiated cases(Ⅲ grade)was significant(P<0.05/3). Conclusion: High expression of HCV gene can be seen in tissues of extrahepatic bile duct carcinoma. Loss of CD81 may be related to the differentiation of extrahepatic bile duct carcinoma.