We report two cases with recurrent non-small cell lung cancer (NSCLC) successfully treated with cisplatin and S-1 after multiple chemotherapy. A 64-year-old woman was diagnosed with adenocarcinoma, yield-T4N2M1, stage IV. She was treated with cisplatin 60 mg/m(2) (day 8) and S-1 80 mg/m(2) (days 1-21) as sixth-line chemotherapy after treatment with paclitaxel and irinotecan, cisplatin and gemcitabine, docetaxel, gefitinib, and vinorelbine. Chest computed tomography (CT) showed partial response of recurrent tumors. Another woman (56 years old) was diagnosed with adenocarcinoma, yield-T0N1M1, stage IV. She was also treated with cisplatin and S-1 as fourth-line chemotherapy after treatment with nedaplatin and gemcitabine, docetaxel and irinotecan, and gefitinib. Chest CT showed a partial response of recurrent tumors. Additionally, we retrospectively reviewed 10 cases with recurrent NSCLC treated with cisplatin and S-1 during the same period. Grade 3 to 4 hematologic toxicity included neutropenia in 30% of these 10 patients, thrombocytopenia in 20%, and anemia in 60%. Grade 3 non-hematologic toxicity included hyperglycemia and hyponatremia in 20% of the 10 patients. All side effects were manageable and there was no case of treatment-related death. Cisplatin combined with S-1 could be an option for recurrent NSCLC.