Objective:To investigate the safety and effect of complete mesocolie excision (CME) combined with arterial infusion chemotherapy (AIC) and intra-peritoneal interstitial sustained-release chemotherapy (IPISRC). Methods:A total of 104 patients were classified under the experimental group and underwent CME combined with AIC and IPISRC. The other 98 patients were classified un-der the control group and only received radical surgery. Pre-and post-operative blood routine examinations, as well as liver and kidney function tests, were conducted for both groups. Post-operative adverse reactions and incidence of complications were recorded. Cancer and para-neoplastic tissues were sampled in experimental group. The post-surgery 5-fluorouracil (5-FU) concentration in the drainage fluid as well as those in the peripheral blood , were determined. Three-year follow-ups were conducted, during which the local recur-rence rate, liver metastasis, progression-free survival rate, and total survival rate were recorded. Results: No significant differences were found in the white blood cell count, hemoglobin count, liver and renal functions of the patients before and after the surgery, and rate of adverse reaction and complications between the two groups after surgery (P>0.05). In experimental group , the 5-FU concentra-tion was significantly higher in the cancer tissues than in the para-neoplastic tissues . The 5-FU concentration in experimental group was also significantly higher in the intra-peritoneal drainage liquid and reached its peak in the peripheral blood on day 3 post-surgery . Local recurrence and liver metastasis rates were significantly lower in experimental group than those in control group, whereas the pro-gression-free and three-year overall survival rates were significantly higher in experimental group than in control group (P<0.05). Con-clusion:The tharepy of pations of experimental goup is safe and effective. This method significantly improves the progression-free and three-year survival rates of the patients as well as significantly reduces the local recurrence and liver metastasis rates of colon cancer.