Introduction: In this study, the efficacy and safety of pemetrexed alone and platinum-pemetrexed combination chemotherapy were evaluated in patients who have demonstrated progression after the first-line treatments in advanced non-small cell lung cancer (NSCLC). Material and Method: 263 patients, who were diagnosed NSCLC in years 2008 - 2014, were assessed retrospectively in single center. Patients were given pemetrexed 500 mg/m2, and the ones receiving combined treatment were given pemetrexed 500 mg/ m2 and cisplatin 75 mg/m2 or carboplatin area under the curve 5 according to the Calvert formula (AUC 5 ) once in every 21 days. Results: One hundred ninety (72%) of the patients had received pemetrexed, seventy three (28%) of the patients had received platinum- pemetrexed. Median PFS (progression-free survival) was 2 months (95% CI, 1. 6 - 2.4 ) for pemetrexed arm versus 4 months (95% CI, 2.6 to 5.3 ) for platinum- pemetrexed arm (p=0.001). The HR ( hazard ration) for disease progression was 0.45 (95% CI, 0.25 to 0.65) in favor of the combination arm (p=0.001). Median OS (overall survival) was 7 months (95% CI, 5.9 - 8 ) for pemetrexed arm versus 10 months (95% CI, 8 to 11.9 ) platinum-pemetrexed arm, respectively (p=0.001). The 1-year survival rate was 24% and 42% for pemetrexed arm and combination arm, respectively. Toxicities in both arm was manageable. Conclusion: Our study has shown that adding platinum compound to second-line pemetrexed chemotherapy significantly increases ORR (overall response rate), PFS and OS in patients with advanced NSCLC after having received first-line platinumbased chemotherapy.