Objective To investigate the effect,survival time and toxicity of S-1 monotherapy on advanced non-small-cell lung cancer with acquired drug resistance of gefitinib.Methods Patients with pathologically confirmed stage Ⅳ lung adenocarcinoma who had had disease control with gefitinib were retrospectively reviewed.After acquired drug resistance,patients received S-1 orally administered at 40 mg/m2 twice a day for 14 days followed by a 7 days rest period.The efficacy and toxicities were observed.Results In the periord of S-1 monotherapy,three patients achieved partial response (PR),and the overall response rate (ORR) of eligible patients was 20％ (3/15),Disease control rate was 60％ (9/15).Median progression-free survival was 205 days (95％ CI:9.174-400.826 days),whereas median survival time was 270 days(95％ CI:262.623-277.377 days).Overallsurvival and PFS in patients with disease control (311 days and 239 days,respectively) were longer than those of patients with disease progression (110 days and 50 days,respectively ; P ＜ 0.05).Survival times was not related with the sex,age,eastern cooperative oncology group performance status and ORR.The most common toxicities of grade 3 or 4 was diarrhea,the incidence was 13.3 ％.Conclusions S-1 monotherapy in the treatment of advanced non-small-cell lung cancer with acquired drug resistance of gefitinib,can make part of the patients acquire remission again,prolong the survival time,and the toxicity is tolerable.