OBJECTIVE： To compare the efficacy and safety of gio combined with oxaliplatin （SOX） versus 5-fluorouracil （5-FU） combined with calcium folinate and oxaliplatin （mFOLFOX6） in the treatment of diffuse  advanced gastric cancer. METHODS： The data of 128 patients with diffuse advanced gastric cancer was retrospectively analyzed and patients were divided into SOX group （66 cases） and mFOLFOX6 group （62 cases） by different medication. SOX group received Gio capsule after breakfast and dinner，which was ＜1.25 m2，40 mg，1.25-1.5 m2， 50 mg，＞1.5 m2， 60 mg， d1-14+130 mg/m2 Oxaliplatin for injection， intravenously， d1；3-week was regarded as a treatment course， the efficacy was evaluated every 2 courses， and it lasted a maximum of 8 courses but a minimum of 2 courses. mFOLFOX6 group received 85 mg/m2 Oxaliplatin for injection， intravenously， d1+200 mg/m2 calcium folinate， intravenously， d1+400 mg/m2 5-FU for injection by rapid intravenous injection， d1， then 2 400 mg/m2 5-FU， maintaining 46 h by continuous infusion. 2-week was regarded as a treatment course， the efficacy was evaluated every 3 courses， and chemotherapy was conducted in a maximum of 12 courses but a minimum of 3 courses. Clinical efficacy， time to progression， survival time and incidence of toxicities in 2 groups were observed. RESULTS： The objective response rate，time to progression and median survival time in SOX group was significantly higher than mFOLFOX6 group， the difference was statistically significant （P＜0.05 or P＜0.01）. There was no significant difference in the disease control rate and incidence of toxicities in 2 groups（P＞0.05）. CONCLUSIONS： The efficacy of SOX is superior to mFOLFOX6 in the treatment of diffuse advanced gastric cancer， it can prolong the survival time， with similar safety.