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Objective To investigate the safety and long-term clinical effect of intraperitoneal implantation of sustained releasing5-fluorouracil in patients with advanced colorectal cancer during radical resection.Methods A total of 202patients with advanced colorectal cancer undergoing radical operation were randomly divided into experimental group(98cases ,intraoperative intraperitoneal implantation of sustained-release 5-fluorouracil 600mg as local chemotherapy) and control group(104 cases,without local chemotherapy).The clinical data of two groups were compared including toxicity, complications, local recurrence rate, distant metastasis, disease free survival and1,3,5-year survival rate.Results Both groups of patients were followed up for more than five years, the longest follow-up time was 7.5 years.Bone marrow suppression ,hepato-renal function, postoperative anastomotic leakage, pelvic effusion, incision infection, the incidence of intestinal obstruction, venting time and hospital stay after operation(days) between two groups had no statistical significant difference.Locoregional recurrence and liver metastasis rate were decreased significantly in experimental group (P =0.04 and 0.04).Extensive peritoneal metastasis, and other organ metastasis rate had no significant difference between two groups.1,3, 5-year survival rate in the experimental group were high than the control group(95.92% vs87.50%, 77.55% vs64.42% and56.12% vs40.38%), which had significant difference.Disease flee survival (DFS) of the experimental group was higher than control group (x 2 =5.00, P =0.025).Conclusions Intraperitoneal implantation of sustained-release5-fluorouracil is safe for advanced colorectal cancer during redical resection, which can reduce locoregional recurrence rate and liver metastasis rate.The long-term efficacy was reliable and long-term survival and diseasefree survival rate can be improved.