Objective: The aim of this study was to analyze and compare the recent efficacy and toxicity of a three-drug platinum-based regimen (A regimen): [cisplatin (DDP) + gemcitabine (GEM) + vinorelbine (NVB)] and a two-drug combination without a platinum drug (B regimen): GEM + NVB, which were used to treat 55 advanced non-small cell lung cancer (NSCLC) patients, in a bid to provide a guidance for clinical treatment. Methods: Twenty-four cases of advanced NSCLC (stage III-IV) patients were treated with A regimen (DDP 35 mg/m2 d1-3; GEM 1250 mg/m2 d1, 8 ). The other 31 cases were treated with B (GEM 1250 mg/m2 d1, 8; NVB 25 mg/m2 d1, 8 ). Repeat every 3 weeks for 6 courses. Results: In A regimen group, the overall response rate was 45.8% (CR + PR = 11), median response time was 5.5 months, median survival time was 11 months and 1-year survival rate was 41.7%. In B regimen group, the overall response rate was 48.4% (CR + PR = 15) and median re-sponse time, survival time and 1-year survival rate were respectively 6.5 and 10 months and 41.9%. The major toxicities were nausea/vomiting, myelosuppression in A regimen group, myelosuppression and phlebitis in B regimen group, respectively. Conclusion: A regimen and B regimen for advanced NSCLC have similar response rate (P > 0.05). B regimen, a two-drug combination without a platinum drug is of less toxicity and more safety than A regimen, a three-drug platinum-based regimen and is recommended to be a regimen in the first-line treatment for advanced NSCLC.