Abstract: Objective To compare the efficacy and toxicity of pemetrexed plus cisplatin regimen and vinorelbine plus cisplatin regimen as the firstline treatment of advanced nonsmall cell lung cancer （NSCLC）. Methods In a retrospective study， 68 patients with advanced NSCLC receiving pemetrexed or vinorelbine plus cisplatin as the firstline chemotherapy from January 2008 to December 2010 were enrolled. Subgroup and chemotherapy regimen were： PC regimen group（n=32， pemetrexed 500mg／m²， d₁; cisplatin 25mg／m²， d₁-d₃）and NP regimen group（n=36， vinorelbine 25mg／m²， d₁， d₈; cisplatin 25mg／m²， d₁-d₃）. Three weeks was a cycle. The efficacy was evaluated every 2 cycles. Results All patients were available for the objective response evaluation， but no complete response was observed in both groups. No significant difference was found between PC regimen group and NP regimen group on the objective response rate （40.6％ vs. 36.1％）， disease control rate （71.9％ vs. 61.1％） and median time to progress （6.2 vs. 5.2 months）. There was a higher incidence of grade 3-4 leukopenia and neutropenia in the NP regimen group compared with the PC regimen group （P＜0.05）. Conclusion Pemetrexed plus cisplatin shows similar efficacy and less toxicity compared with vinorelbine plus cisplatin as the firstline treatment of advanced NSCLC.