Objective: To compare the clinical efficacy of oxaliplatin plus tegafur-gimeracil-oteracil potassium (S-1) and XELOX (oxaliplatin+capecitabine) regimen in adjuvant chemotherapy for postoperative gastric cancer patients. Methods: Eight-one stomach cancer patients were randomly assigned to observational group (n=41) and control group (n=40) after surgery. Patients in observational group received oxaliplatin+S-1 regimen, while those in control group were treated with XEOLX regimen. Results: The 1- and 2-year recurrence-free survival (RFS) for observational group was 51.3% and 61.5%, and for control group was 25.6% and 20.5%, while the 1- and 2-year overall survival (OS) for observational group was 64.1% and 69.2%, and for control group was30.8% and 25.6% respectively, and all differences had no statistical significance (P=0.361, 0.591; P=0.631, 0.615). The toxic and side effects seen in both groups were mainly myelosuppression, gastrointestinal reactions, hand-foot syndrome, oral mucositis, and peripheral neuropathy as well as hepatic and renal function damage, among which, the incidence of hand-foot syndrome in control group was significantly higher than that in observational group (P=0.001); all the toxic and adverse reactions were resolved by symptomatic treatment. Conclusion: Oxaliplatin+S-1 regimen has an efficacy equivalent to XELOX regimen in adjuvant chemotherapy for postoperative gastric cancer.