Abstract： Objective To investigate the significance of tamoxifen in the combination chemotherapy of human multidrug-resistant bile duct carcinoma cell line (QBC939/ADM) and its mechanism. Methods The QBC939/AI)M was established, through exposure to gradually increased and the high and low alternated concentration of ADM persistently. The QBC939 and the QBC939/ADM were effected by single ADM, MMC, VDS or jointly with TAM. Drug sensitivity was measured by MTT. Growth cycle and apoptosis were performed by FCM. The level of their P-gp was detected by IHC. The content of ADM in the human cholangiocarcinoma cell line QBC939 was observed by FCM. Results The inhibitive rate of ADM, MMC, VDS to QBC939/ADM was rather lower than to QBC939. With the use of TAM, their chemotherapy effects were apparently enhanced and the apoptosis ratio increased comparably. The IHC results showed that the level of P-gp on the QBC939/ ADM was overexpressed, and the content of ADM in the QBC939/ADM group was much lower. Effected with the high content of TAM(10 μmol/L), the level of P-gp on the QBC939/ADM was decreased, with the content of ADM in the QBC939/ADM group increased comparably. TAM could both improve the chemotherapy effects of the two types of the cell, but the effect of the QBC939/ADM group was more apparent. Conclusion TAM can enhance the depressant effect of chemotherapy to both the two types of the cell, and increase the content of ADM in the QBC939/ADM group. TAM can be combined with the overexpressed P-gp.