Objective: To investigate the feasibility, safety and short-term clinical efficacy of early hyperthermic intraperitoneal chemotherapy (HIPEC) after radical resection of T4 colorectal cancer. Methods: The clinical data of 96 patients with T4 colorectal cancer treated from January 2011 to June 2013 were retrospectively analyzed. Of the patients, 48 cases began to receive HIPEC from postoperative day 5 or 6 (once daily for a total of 3 sessions), and then underwent the first systemic infusion of mFOLFOX6 regimen within postoperative one month, for a total of 6 cycles (HIPEC group), and another 48 cases only underwent systemic chemotherapy of the same regimen (control group). The incidence of adverse effects and complications, and the 1- and 2-year recurrence and survival rate as well as the quality of life of the two groups of patients were compared. Results: HIPEC and systemic chemotherapy were all successfully performed. There were no surgical deaths or complications such as incisional wound infection, anastomotic leakage and adhesion intestinal obstruction in either group. There were no significant differences in incidence of myelosuppression, nausea, vomiting and liver dysfunction between the two groups (all P>0.05). The 1- and 2-year recurrence rate in HIPEC group were significantly lower than those in control group (2.1% vs. 20.8%; 6.3% vs. 31.3%, P<0.05). There was no difference in 1-year survival rate between the two groups (P>0.05), but the 2-year survival rate was significantly higher in HIPEC group than that in control group (81.3% vs. 58.3%, P<0.05). The ratio of patients with increased score of quality of life in HIPEC group was significantly higher than that in control group (75.0% vs. 25.0%, P<0.05). In HIPEC group, the median survival time of patients with colon cancer was significantly longer than that of patients with rectal cancer (32 months vs. 18 months, P<0.05). Conclusion: Early postoperative HIPEC for T4 colorectal cancer following radical resection is safe and feasible. It can effectively reduce peritoneal recurrence and metastasis, improve the short-term survival and quality of life of the patients, and has no obvious adverse effects.