ObjectiveTo evaluate the efficacy and safety of various hyperthermic intraperitoneal chemotherapy (HIPEC) combined with systemic chemotherapy in patients with malignant ascites (MA) secondary to gastrointestinal malignancies.MethodsClinical data of 50 patients with advanced gastrointestinal malignancies and MA treated with HIPEC plus best supportive care (BSC) at Shanghai Tenth People's Hospital, Tongji University from January 2019 to January 2023 were retrospectively analyzed. Short-term therapeutic outcomes were assessed using the Chinese Clinical Guidelines for Hyperthermia in Oncology (2022 Edition), while long-term survival was evaluated via Kaplan-Meier analysis.ResultsThe treatment responses included complete response in 5 cases (CR: 10%, 5/50), partial response in 6 cases (PR: 12%, 6/50), stable disease in 30 cases (SD: 60%, 30/50), and progressive disease in 9 patients (PD: 18%, 9/50), yielding an objective response rate (ORR) of 22% and disease control rate (DCR) of 82%. The median progression-free survival (PFS) and overall survival (OS) was 7.39 months and 12.26 months, respectively. Analysis of tumor markers before and after treatment revealed a negative correlation between therapeutic efficacy and CA125 levels (P=0.001).ConclusionHIPEC demonstrates clinically meaningful efficacy and survival benefits with a favorable safety profile in advanced gastrointestinal malignancies complicated by MA. Lobaplatin-based regimens exhibites superior therapeutic outcomes compared to cisplatin or paclitaxel. Serum CA125 may serve as a predictive biomarker for poor prognosis.