Objective: To evaluate the clinical efficacy and safety of hyperthermic intraperitoneal chemoperfusion therapy for malignant ascites. Methods: The randomized controlled trials (RCTs) comparing hyperthermic intraperitoneal chemoperfusion therapy and normothermic intraperitoneal chemoperfusion therapy for malignant ascites were collected by computer-based search in the national and international online databases, along with retrieval from other sources. After literature screening, data extraction and quality evaluation by two independent reviewers according to the protocol, Meta-analyses were performed by using the RevMan 5.2 software. Results: Fifteen RCTs were finally included, involving 998 patients with 506 cases undergoing hyperthermic intraperitoneal chemoperfusion therapy (hyperthermic perfusion group) and 492 cases undergoing normothermic intraperitoneal chemoperfusion therapy (normothermic perfusion group). Meta-analysis showed that the 1-year survival rate, total effective rate and complete remission rate in hyperthermic perfusion group were all better than those in normothermic perfusion group, and all differences reached statistical significance (all P<0.05); the incidence of nausea and vomiting, bone marrow inhibition, and hepatic and kidney injury were lower in hyperthermic perfusion group than those in normothermic perfusion group, but the differences had no statistical significance (all P>0.05), while the incidence of abdominal pain in hyperthermic perfusion group was higher than that in normothermic perfusion group, with statistical difference (P<0.05). Conclusion: Hyperthermic intraperitoneal chemoperfusion therapy is safe and effective in treatment of malignant ascites, and can also improve the survival of the patients. However, its long-term safety requires further verification by more RCTs with large sample size and of high-quality.