Abstract: Objective To evaluate the efficacy and safety profile of S-1 combined with oxaliplatin (SOX) for the treatment of locally advanced unresectable or metastatic gastric cancer. Methods Oxaliplatin was given by intravenous drop (130 mg/m²) on the first day, while S-1 was given orally (40 mg/m², b.i.d.) for 14 days followed by a 7-day rest. This schedule was repeated every 3 weeks. Treatment was continued until disease progressed or intolerable toxicity occurred. Results Sixty-one patients were enrolled, all were assessable for safety and survival.Forty-six patients were objectively assessable for tumor response. The response rate was 56.5%, and the disease control rate was 76.1%. The median progression-free survival time was 7.5 months(95% CI: 5.1-9.7 months), the 1-year survival rate was 62.9%, and the estimated median survival time was 16 months(95% CI:13.2-18.8 months). The major grade 3/4 toxic effects were neutropenia (13.1%) and thrombocytopenia (18%)decreased. Conclusion These findings indicate that SOX regimen is feasible and shows promising efficacy against advanced gastric cancer.