Objective To evaluate clinical efficacy of mFOLFOX6 combined with aspirin in treatment of advanced gastric cancer following perioperative period of laparoscopic distal subtotal gastrectomy. Methods One hundred and seven patients with advanced gastric cancer were assigned to observation group (57 cases) and control group (50 cases). The patients in the observation group received the mFOLFOX6 chemotherapy and regular intake of aspirin (100 mg/d) and the control group received the mFOLFOX6 chemotherapy alone. The recurrence or metastasis rate, rate of disease progress, toxicity, median survival time, and 3-year survival rate were compared between the observation group and the control group. Results ① There were no significant differences in the gender, age, pathological type, and so on between the observation group and the control group (P>0.05). ② The rates of toxicity such as the white blood cell reduction, granulocyte reduction, thrombocytopenia had no significant differences in these two groups (P>0.05). ③ The follow-up time was 4–45 months with an average 3.5 years, the rate of disease progress was lower (P=0.032), the median survival time was longer (P=0.043), the cumulative 3-year overall survival (P=0.015) and the cumulative 3-year disease-free survival (P=0.037) were better in the observation group as compared with the control group. Conclusion Preliminary results in this study show that mFOLFOX6 regimen combined with low-dose aspirin could significantly improve efficacy of advanced gastric cancer following perioperative period of laparoscopic distal subtotal gastrectomy, reduce rate of disease progress, and improve survival rate without increasing side effects.