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Background and objective Platinum-based chemotherapy is considered the standard treatment of advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the efficacy and safety of gemcitabine plus oxaliplatin (GO) versus gemcitabine plus cisplatin (GP) regimens as the 1st line chemotherapy for elderly patients with advanced NSCLC. Methods Sixty-six advanced NSCLC patients confirmed with pathology or cytology, who had not received treatment, were randomly divided into GO group (The patients received gemcitabine 1,000 mg/m2 on day 1 and day 8 and oxaliplatin 130 mg/m2 on day 1 by intravenous infusion, with 21 days as one cycle) and GP group (The patients received gemcitabine 1,000 mg/m2 on day 1 and day 8 and cisplatin 25 mg/m2 on day 1, day 2 and day 3) by intravenous infusion, with 21 days as one cycle). All patients who received 2 or more cycles could be evaluated. Results There were no statistical differences between GO and GP groups in the efficiency of disease (36.4% vs 40.6%, P=0.801), the median progression-free survival (24 weeks vs 18 weeks, P=0.565), the median survival time (44 weeks vs 36 weeks, P=0.918), but anemia at grade III and IV (0 vs 33.3%, P<0.001) and nausea/vomiting at grade III and IV (0 vs 27.3%, P=0.004) were significantly different. Conclusion The clinical efficiency of GO and GP regimens as the 1st line chemotherapy for advanced NSCLC in elderly patients was similar, but the toxicity of GO regimen has the tendency to be more tolerable and safer.