Abstract: Objective: To investigate the expression and clinical significance of drug fast-related proteins and p53, bcl-2 genes in lung cancer tissue. Methods: The expression of P-glycoprotein (P-gp), multidrug resistance-GAP-associated proteins (MRP), lung resistance protein (LRP), glutathione S transferases (GST), p53 and bcl-2 genes in lung carcinoma tissue from 73 untreated patients was measured by immunohistochemistry technique, respectively. Results: The protein expressions of P-gp, LRP, MRP+LRP and P-gp+p53 in NSCLC were obviously higher than that in SCLC (P<0.05). The protein expression of MRP, LRP, MRP+LRP, MRP+LRP+GST-π and MRP+LRP+P-gp+GST-πin adenocarcinoma was respectively higher than that in SqCa, SCLC (p<0.05), the co-expression of MRP +GST-π higher than that in SqCa (p<0.01), the co-expression of P-gp+p53 higher than that in SCLC (p<0.05) and the expressions of bcl-2 lower than that in SqCa and SCLC (p<0.05). The expression of P-gp, P-gp+p53 and P-gp+bcl-2 in SqCa showed was respectively higher than that in SCLC (p<0.05). The expression of P-gp showed a positive correlation with p53 and bcl-2 (p<0.05). The expressions of p53 and bcl-2 also showed positive correlation (p<0.01). The expressions of MRP showed positive correlation to GST-π(p<0.05). Conclusion: Multidrug resistance of lung cancer is a process involved in polygene and multiple pathways, the expression and co-expression of P-gp, LRP, MRP, GST-π, p53 and bcl-2 can be an indicatrix to detect the primary drug resistance of lung cancer.