Objective To evaluate the efficacy and safety of intraoperative mesenchymal chemotherapy with 5-FU implants in radical gastrectomy of advanced gastric cancer. Methods From January 2008 to September 2009， 102 patients with historically proven advanced gastric cancer were enrolled in our department and were allocated to undergo either radical gastrectomy and intraoperative mesenchymal chemotherapy with 5-FU implants 800 mg（treatment group， n=51）， or radical gastrectomy alone （control group， n=51）. The postoperative complications and recurrence rate between two groups were compared. Results There were no significant differences on the volume of abdominal cavity drainage， count of white blood cells， albumin level， and gastrointestinal adverse events between the two groups （P＞0.05）. After a median follow-up of 28 months， the local recurrence rate was lower among patients in treatment group than that in control group （16.3% vs. 39.1%， P＜0.05）， the survival rate of 3-year was higher in treatment group than that in control group （85.8% vs. 67.3%， P＜0.05）. Conclusions Compared with the control group， there are no significant adverse reactions on patients with advanced gastric cancer who were implanted fluorouraci1 implants during operation， which can reduce local recurrence rates and improve the survival rates.