Objective：To investigate the expression of P-glycoprotein （P-gp）, multidrug resistance-related protein （MRP）, lung resistance-related protein （LRP）, P53 and c-erbB-2 in untreated non-small cell lung cancer （NSCLC） and their relationship with each other. Methods： The expression of P-gp, MRP, LRP, P53 and c-erbB-2 was detected in the carcinoma tissues of 78 NSCLC patients and 15 adjacent normal lung tissues （5 cm apart from tumors） by means of immunohistochemistry. Results： The positive rates of P-gp, MRP, LRP, P53 and c-erbB-2 in tumor tissues were 65.4 %, 39.7 %, 56.4 %, 53.8 % and 43.6 %, respectively, all significantly higher than those in normal tissues（P〈0.05）. There was also significant difference in MRP and LRP expression between different pathologic types of NSCLC（squamous cell carcinoma, adenocarcinoma, large cell carcinoma） （P= 0. 008 and G0. 001, respectively）. Expression of LRP and P53 was also significantly different between different degrees of pathological differentiation （well, moderate, poor） （P=0. 025 and 0. 026, respectively）. The expression of c-erbB-2 was correlated with those of P-gp, MRP, LRP and P53 （Spearman R=0. 317, 0. 401, 0. 519 and 0. 341, respectively;P=0. 005, G 0. 001, G0.001 and =0.002, respectively） ; the expression of P53 was correlated with that of MRP （Spearman R=0. 260,P= 0. 022） ; and the expression of LRP was correlated with that of MRP （Spearman R = 0. 371, P= 0. 001 ）. Conelusion： Overexpression of P-gp, MRP, LRP, P53 and c-erbB-2 may play a cooperative role in the drug resistance and development of NSCLC.