Background Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric cancer.We conducted a Phase Ⅱ trial to determine the efficacy and safety of S-1 plus oxaliplatin (SOX regimen) as first-line chemotherapy for patients with unresectable locally advanced or metastatic gastric cancer.Methods Eligible patients had measurable lesions and no previous history of chemotherapy (except adjuvant chemotherapy).Oxaliplatin was administered intravenously at a dose of 130 mg/m2 on day 1.S-1 was administered orally in doses of 80,100,or 120 mg/d according to body surface areas of ＜1.25 m2,1.25-1.5 m2,or ＞1.5 m2 respectively;the total dose was divided into two daily doses on days 1-14.Treatments were repeated every 3 weeks until disease progression or intolerable toxicity occurred.Results Forty-three patients were enrolled in the study.All were assessable for efficacy and adverse events.The objective response and disease control rates were 55.8％ and 76.7％ respectively.The median follow-up time was 16.5 months.The median progression-free survival time was 7 months (95％ Cl,5.8-8.2 months) and the median overall survival time was 16.5 months (95％ Cl,9.7-23.3 months).The one-year survival rate was 54.2％.Major adverse reactions were grade 3/4 neutropenia (9.3％) and thrombocytopenia (20.9％).Conclusion The SOX regimen with oxaliplatin at a dose of 130 mg/m2 was found to be effective and safe as a first-line chemotherapy in Chinese patients with advanced gastric cancer.