Objective To evaluate the efficacy and toxicity of S-1 combined with three-dimensional conformal radiotherapy （3D-CRT） in treatment of advanced gastric cancer. Methods A total of 83 patients were divided into two groups：43 cases with concurrent chemoradiotherapy （treatment group） and 40 cases with combined chemotherapy（control group）. The fractionated dose of 3DCRT was 2Gy，5f／w. The total dose was 40-50Gy. S-1 was concurrently taked orally，40-60mg po，twice a day and 6 weeks was one cycle. Forty gastric patients in control group were treated by the firstline chemotherapeutic regimens such as ECF，DCF，FOLFOX，FOLFIRI regimens, etc. Results A total of 82 patients could be evaluated. In treatment group，3 cases achieved CR，with PR in 21 cases，SD in 14 cases，PD in 4 cases. The response rate（RR） was 57.1％（24／42）. In control group，2 cases achieved CR，with PR in 15 cases，SD in 15 cases，PD in 8 cases. RR was 42.5％（17／40）.There were no statistical difference between two groups （P＞0.05）.The one year overall survival rate of treatment group and control group was 23.8％ and 20.0％ with no statistical significance（P＞0.05）. Compared with control group，the subjective symptoms of treatment group improved significantly（81.0％ vs. 50.0％，P=0.008）. The major adverse events were hematological toxicity，hepatic function damage，radioactive pancreatitis and gastrointestinal reaction. The incidences of grade 3/4 neutropenia, grade 1/2 elevated transaminase and grade 3/4 nausea and vomiting in treatment group were lower than those in control group（P＜0.05）. Conclusion S-1 combined with 3D-CRT is a promising and safe treatment to improve the quality of life of patients with advanced gastric cancer，which deserves further clinical study.