Objective: To investigate the safety and feasibility of laparoscopic colorectal cancer resection cancer in combination with intraoperative intraperitoneal hyperthermic perfusion chemotherapy (IHPC). Methods: One-hundred and twenty patients with advanced colorectal cancer were randomly divided into treatment group and control group with 60 cases in each group. All patients underwent laparoscopic colorectal cancer resection. Patients in treatment group received intraoperative IHPC combined with postoperative systemic chemotherapy with mFOLFOX6 regimen, while those in control group were given postoperative systemic chemotherapy with mFOLFOX6 regimen only. The surgery-related parameters, postoperative recovery, complications, adverse reactions, local recurrence and distant metastasis between the two groups of patients were compared. Results: There was no significant difference with respect to surgery-related parameters, postoperative recovery and incidence of postoperative complications between the two groups (all P>0.05). The incidences of postoperative hypoalbuminemia and hyponatremia were significantly increased in treatment group compared with control group (20.0% vs. 6.7%; 15.0% vs. 3.3%, both P<0.05), while the rates of peritoneal local recurrence and distant metastasis were significantly lower in treatment group than those in control group (6.7% vs. 18.3%; 8.3% vs. 23.3%, both P<0.05). The short-term overall survival rates were similar between the two groups (P>0.05). Conclusion: IHPC in laparoscopic colorectal cancer resection followed by postoperative systemic chemotherapy is safe and reliable, and has some efficacy in reducing local recurrence and distant metastasis.