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All patients with advanced non-small-cell lung cancer experience disease progression after first-line chemotherapy. The median survival is between 4 and 5 months without second-line chemotherapy. There are currently three agents approved for treating patients who progress after one prior regimen: docetaxel, pemetrexed and erlotinib. Evidence of other treatment with drugs, including S-1 is unclear.All patients had adequate hematology and biochemistry parameters with a good performance status and advanced non-small-cell lung cancer. They are already treated with guideline recommended chemotherapy regimens. We carried out a retrospective analysis of patients who received treatment with S-1 80 mg/m2 (d1–28) or S-1 80 mg/m2 (d1–14) and CBDCA AUC 5 (d1).From April 2010 through February 2012, five patients were received therapy with S-1 and four with CBDCA + S-1. The disease control rate after 12 weeks was 89%, but there were no PR. The main toxicity was myelosuppression, gastrointestinal disorders. One case of grade 4 mucosal damage, one case of grade 3 diarrhea and one case of grade 3 thrombocytopenia were observed. Other adverse events were mild and could be tolerated.Concerning patients with a good PS at the time of disease progression, chemotherapy using S-1 may be associated with a good disease control rate and an acceptable toxicity in spite of finishing guideline recommended chemotherapy. The prospective study for third- or fourth-line chemotherapy with S-1 should be considered.