Objective To compare the efficacy and resistance between S?1 combined with radiotherapy and S?1 alone in the treatment of elderly patients with locally advanced gastric cancer. Methods Fifty?eight elderly patients with unresectable locally advanced ( stage Ⅲ) gastric cancer were randomly and equally divided into S?1 combined with concurrent radiotherapy group ( experimental group ) and S?1 alone group ( control group ) . The experimental group received 4 cycles of S?1 treatment with each cycle containing two?week oral administration of S?1 at a dose of 40 mg/m2 twice a day followed by one?week drug withdrawal. Gastric intensity?modulated radiotherapy was performed concurrently with a dose of 45 Gy ( 1. 8 Gy per fraction) . The control group received the same dose of S?1 alone. Short?term outcomes and adverse reactions were evaluated in the two groups. Comparison was made by chi?square test. Results All patients completed the planning treatment. The experimental group had significantly higher objective response, disease control, and symptom remission rates than the control group ( 52% vs. 24%, P=0. 03;76% vs. 45%, P=0. 016;86% vs. 48%, P=0. 005) . There were no significant differences in the incidence of nausea and vomiting, anorexia, leukopenia, diarrhea, or thrombocytopenia between the two groups ( all P>0. 05) . Conclusions S?1 treatment combined with concurrent radiotherapy improves the short?term outcomes and causes tolerable toxicities in the treatment of elderly patients with locally advanced gastric cancer.