Objective To study the clinical efficacy of intraperitoneal injection of Endostar, cisplatin and recombinant human interleukin-2 (rhIL-2) combined with hyperthermia in the treatment of malignant peritoneal effusion caused by malignant tumor.Methods A total of 60 patients with malignant abdominal effusion admitted to the Affiliated Hospital of Hebei University of Engineering between January 2017 and June 2020 were selected. They were divided into observation group (n=30) and control group (n=30). The observation group received intraperitoneal injection of Endostar 30 mg + cisplatin 60 mg + rhIL-2 2×10⁶ IU and combined with microwave hyperthermia, while the control group received intraperitoneal injection of cisplatin 60 mg + rhIL-2 2×10⁶ IU and combined with microwave hyperthermia. The clinical efficacy and side effects of the two groups were analyzed.Results The total effective rate of the observation group (90.0%) was significantly higher than that of the control group (73.3%) (P=0.03). The improvement rate of the quality of life was also higher in the observation group (80%) than in the control group (60%) (P=0.043). The main adverse reactions in both groups included fever, nausea and vomiting, poor appetite, fatigue, thrombocytopenia and anemia, but no statistical differences were found in their incidence rates between the two groups (P=0.55).Conclusion Intraperitoneal injection of Endostar, cisplatin and rhIL-2 combined with hyperthermia is safe and effective in the treatment of malignant peritoneal effusion. This treatment method can significantly reduce the pain of patients and improve the quality of life. The side effects are mild and controllable. So it is worth clinical promotion.