PURPOSE: To evaluate the relationship between the expressions of p53, bcl-2, bax, and p-glycoprotein and the chemotherapeutic response seen in patients with advanced NSCLC. MATERIALS AND METHODS: Forty-four patients pathologically proven as NSCLC were reviewed. They had undergone at least two cycles of the same chemotherapeutic agents (cisplatin 60 mg/m2 day 1+ vinorelbine 25 mg/m2 day 1, 8, 21-day cycle) and the clinical response was evaluated by WHO criteria. The expressions of p53, bcl-2, bax, and p-glycoprotein were determined by immunohistochemistry. RESULTS: Patients recorded as CR (2/44) and PR (20/44) were classified as the responder group (22/44) and stable (17/44) and progression (5/44) as the non-responder group (22/44). Positive expression of p53, bcl-2, bax, and p-glycoprotein were 84.1%, 65.9%, 88.6%, and 61.4% respectively. The expression score of p53 was significantly higher in the non-responder group than that seen in the responder group (8.59+/-1.89 vs 5.32+/-2.15, p<0.05). However, the expression scores of bcl-2, bax, and p-glycoprotein were not significantly correlated with the clinical response. CONCLUSION: This study suggests that p53 gene mutation plays an important role in the clinical response to chemotherapy including cisplatin and vinorelbine. In future investigations, the correlation with the survival time will be studied.