Abstract: Objective: To study the effect of intraperitoneal chemohyperthermia (IPHC) combined with staphyloentero-toxin (SE) on advanced peritoneo-pelvic tumors with malignant ascites. Methods:In the pro -spective and randomized control trial, 100 casesof advanced peritoneo-pelvic tumor with malignant ascites were divided into two groups. Patients in the observation group ( n=50) received IPHC combined with SE. Pa -tients in the control group (n=50) were treated with IPHC alone. The efficacy of the treatment, overall survival (OS), immune condition and side effects were evaluated. Results: The control rate of ascites was 86% (43/50) in the observation group and 68% (34/50) in the control group, with a significant difference ( P=0.032 ). The complete response (CR) rate was 82.5% (33/40) in the observation group and 58.1% (18/31) in the control group after the second treatment. No significant difference was found in OS between the two groups ( P= 0.548 ). A significant difference was found in the improvement of KPS between the two groups (P=0.038 ) with 84% (42/50) in the observation group and 66% (33/50) in the control group. Immune condition was improved in the observation group. The rate of bone marrow suppression was significantly different between the two groups. An 8% decrease in WBC was noted in the observation group while the control group displayed a 24% decrease. An 8% decrease in PLT was observed in the observation group and a26% decrease was noted in the control group. Conclusion:IPHC is a simple, safe and effective treatment method for patients with malig -nant ascites. IPHC combined with SE can reduce toxicity, enhance therapeutic efficacy, reduce frequency of treatment, and improve patients’quality of life.