Abstract: Objective To observe the efficacy and toxicity of an oral anticancer fluoropyrimidine derivative（S-1） for previously treated patients with advanced non-small cell lung cancer（NSCLC）. Methods Sixty advanced NSCLC patients received second-line or further-line chemotherapy previously were enrolled in this study. Thirty cases were given S-1 orally（group A）， the dosage was taken according to body surface， ranging 80mg／d to 120mg／d. Twenty-one days was a cycle. The efficacy and toxicity were evaluated after 2cycle treatment.Another thirty cases were received best supportive care only（group B）. Results In group A， there were no CR and PR case， SD was 18 cases， PD was 12 cases and the disease control rate was 60.0％（18／30）. The toxicity was mild. The main side effects were gastrointestinal reaction and bone marrow suppression. The median progression free survival（PFS） of group A and group B were 2.5 months and 2.0 months， the median overall survival（OS） were 5.0 months and 3.0 months respectively. Between the two groups， the PFS and OS was not statistically different. Conclusion S-1 exhibits modest activity and acceptable toxicity when was used as a third or subsequent line of chemotherapy in patients with advanced NSCLC.