Objective: To assess the overall response rate and toxicity of pemetrexed puls a platinum agent(cisplatin or carboplatin) in the patients with unresectable stage ⅢB/Ⅳ non-small-cell lung cancer(NSCLC). Methods: Sixty-nine chemotherapy-naive patients with stage ⅢB/Ⅳ NSCLC received pemetrexe 500 mg/m2 plus cisplatin 75 mg/m2(n = 47) or pemetrexed 500 mg/m2 plus carboplatin area under the curve of 5 (AUC=5,n = 22) on day 1,one cycle of treatment is 21 days,and the whole treatment lasted 2 to 6 cycles. RECIST 1.0 was used to assess the efficacy of the treatment,and NCI CTC-AE version 3.0 was used to describe adverse events. Results: In the 69 patients,none showed complete response,27 patients showed partial response,24 had stable disease,the overall response rate was 39.1 %,and the disease control rate was 73.9%. There were higher overall response rates and disease control rates in the patients with nonsquamous histology than that of the patients with squamous histology(41.1% vs 30.8% and 76.8% vs 53.8%). Among the 69 patients,the median progression-free survival was 5.3 months,there was no significant difference in progression-free survival (PFS) between the patients with and without squamous histology (4.5 months vs 5.4 months,P > 0.05),but there was a significant difference in PFS between the patients with adenocarcinoma and with squamous cell carcinoma(5.6 months vs 4.5 months,P = 0.03);In multivariate analysis using the Cox regression model,the histology emerged as an independent indicator(P < 0.05). The principal drug-related adverse events were myelosuppression,gastrointestinal response and fatigue,most of which were grade 1 to 2. Conclusion: Pemetrexed plus platinum compunds was safe and efficacious for the treatment of patients with advanced NSCLC,and the nonsquamous histology may be probably associated with better outcomes.