Abstract: Objective To compare the efficacy and safety of S-1 and oxaliplatin（L-OHP） combined with or not with paclitaxel（TAX） for advanced gastric cancer. Methods Fifty-three patients with advanced gastric cancer collected from January 2007 to August 2011 in our department were divided into two groups： group A with 26 patients（TAX 175mg／m2 iv， d1； S-1 40mg／m2 po，bid，d1-d14； L-OHP 85mg／m2 iv， d1） and group B with 27 patients（S-1 40mg／m2 po，bid， d1-d14； L-OHP 130mg／m2 iv， d1）. Twenty-one days was a cycle. The efficacy and side effects of two groups were evaluated. Results Toxicity could be evaluated in all the patients. The response rate could be evaluated in 52 patients. In group A and group B， the response rate was 56.0％ and 40.7％（P=0.271） and the disease control rate was 88.0％ and 63.0％（P=0.037）， respectively. The median time to progress of two group was 10.0 months and 8.0 months（P=0.061）， and the median overall survival was 13.0 months and 10.0months（P=0.060）. The main toxicity were hematological and digestive toxic reactions without statistic significance. There were more neurotoxicity in group B（P＜0.05）， and more alopecia in group A（P＜0.05）. Conclusion The efficacy of S-1 and L-OHP combined with paclitaxel is superior in the disease control rate for advanced gastric cancer compared with S-1 plus L-OHP regimen and the side effects are tolerable. It is worthy of further clinical study.