Abstract： Objective To prospectively evaluate the efficacy and toxicity of irinotecan plus cisplatin (IP regimen) compared with gemcitabine plus cisplatin (GP regimen) as a first-live treatment for advanced non-small cell lung cancer (NSCLC).Methods A total of 63 patients were randomly assigned to two regimens.IP Group (31 patients):irinotecan 100 mg/m2,iv,d1 and d8; cisplatin 25 mg/m2,iv,dl to d3,and 3 weeks a cycle.GP Group (32 patients):gemcitabine 1000 mg/m2,dl and d8; cisplatin 25 mg/m2,iv,d1 to d3,and 3 weeks a cycle.All the patients at least received two cycles of therapy.The response rate (RR),disease control rate (DCR),median time to tumor progression (TTP),median survival time (MST),1-year survival rate,and side effects were observed.Results Among the 31 cases of IP group,8 patients had PR,17 patients had SD and 6 patients had PD.The RR and DCR were 25.8％ (8/31) and 80.6％ (25/31),respectively.The TTP was 6.7 months,MST was 11.2 months and the 1-year survival rate was 45.2％ (14/31).Among 32 cases in the GP group,11 patients had PR,18 patients had SD and 3 patients had PD.The RR and DCR were 34.4％ (11/32) and 90.6％ (29/32),respectively.The TTP was 6.5 months,MST was 11.0 months and the 1-year survival rate was 43.7％ (14/32).The main side effects of the two groups included hematologic toxicities,digestive tract reaction and hair loss.The incidence of diarrhea in the IP group was significantly higher than that in the GP group(P ＜0.05),but the incidence of thrombocytopenia in the GP group was significantly higher than that in the IP group (P ＜ 0.01).Conclusions Our findings demonstrate that the two regimens have similar efficacy as a first-line treatment for advanced NSCLC.The major toxicities of the two regimens are well tolerable.