Abstract: Objective To study the safety and efficacy of postoperative hyperthermic intraperitoneal chemotherapy in patients with progressive colorectal cancer. Methods Clinical data about 143 cases with progressive colorectal cancer underwent surgery in department of general surgery of Chinese PLA General Hospital from July 2013 to July 2014 were reviewed. Patients were randomly divided into observation group (n=72) and control group (n=71). Patients in observation group received hyperthermic intraperitoneal chemotherapy combined with conventional intravenous chemotherapy, while patients in control group only received intravenous chemotherapy. The incidences of adverse reaction of chemotherapy and postoperative complications, 3-year overall survival and metastatic recurrence in patients of the two groups were compared. Results There was no statistically significant difference between the two groups in gender, age, primary tumor location, tumor infiltration depth, lymphatic metastasis, TNM staging, and pathological type. The incidences of adverse reaction of chemotherapy in observation group, including gastrointestinal reaction (Ⅰ -Ⅱ 41.7%,Ⅲ-Ⅳ 13.9%), bone marrow suppression (Ⅰ-Ⅱ 33.3%, Ⅲ-Ⅳ 19.4%), liver function injury (Ⅰ-Ⅱ 38.9%, Ⅲ-Ⅳ 18.1%), were slightly higher than those of control group (Ⅰ-Ⅱ 39.4%, Ⅲ-Ⅳ 15.5%; Ⅰ-Ⅱ 26.8%, Ⅲ-Ⅳ 15.5%; Ⅰ-Ⅱ 36.6%, Ⅲ-Ⅳ 15.5%, all P < 0.05). Complications in observation group, including bleeding, which was slightly lower than that of control group (9.7% vs 9.9%), while leakage and fistula (9.7%), abdominal cavity infection (13.9%), intestinal obstruction (11.1%) were slightly higher than those of control group (8.5%, 11.3%, 8.5%), but no statistical difference was found. The 1-year, 2-year, 3-year recurrence metastasis rates of observation group were 2.8%, 6.9%, 9.7%, and they were less than those of control group (11.2%, 15.5%, 21.1%) without significant difference. The 1-year, 2-year,3-year survival rates of the observation group were 90.3%, 80.6%, 70.8%, lower than those of control group (80.3%, 64.8%, 54.9%), and the differences were statistically significant (All P < 0.05). Conclusion Compared with traditional intravenous chemotherapy, postoperative hyperthermic intraperitoneal chemotherapy combined with intravenous chemotherapy can reduce the recurrence rate and prolong the survival of patients with progressive colorectal cancer.