Abstract: Objective Chemotherapy is the main treatment for advanced gastric cancer, and there is no universally accepted standard chemo-therapy for advanced gastric cancer. The purpose of this study is to observe the effects and adverse reactions of irinotecan combined with tegafur-gimeracil-oteracil potassium capsule (S-1) in the treatment of advanced gastric cancer. Methods Total 24 patients with advanced gastric cancer who meet the entry criteria in the First Affiliated of Anhui Medical University from May, 2013 to May, 2016 were enrolled into this study. The chemotherapy regiment was Irinotecan intravenous drip combined with oral S-1; two or more cycles of chemotherapy were conducted. All patients were expected to four to six cycles of treatment and the effect of chemotherapy was evaluated every two cycles. The efficacy and adverse effects were evaluated. The efficacy of therapy was evaluated according to RECIST, and toxicity effects. SPSS 13. 0software was used for statistical analysis. The analysis of therapy was conducted by using the χ² testing. Results All 24 patients were evaluable, 1 patient reached complete response, 7 patients with partial response, 7 patients with stable disease. The overall response rate was 33. 3%, and the disease control rate was 62. 4%. The major adverse effects were nausea and vomiting, myelosuppression and delayed diarrhea. Most adverse reactions were type Ⅰ/Ⅱ, as type Ⅲ/Ⅳ ere reduction of white blood cells (12. 5%), neutrophil (16. 7%), platelet hemoglobin and Late-onset diarrhea. Conclusion Irinotecan combined with S-1 shows good efficacy and disease control rate in treatment of advanced gastric cancer. Adverse reactions of this treatment are tolerable, and the way of drug delivery is more convenient. It is worthy of further application.