Background and purpose: Lobaplatin, as a traditional chemotherapeutic drug, is widely used in the treatment of malignant tumor. In recent years, its application in the field of hyperthermic intraperitoneal chemotherapy (HIPEC) has garnered increasing attention. This study evaluated the efficacy and safety of lobaplatin-based HIPEC in advanced abdominal metastatic cancer. Methods: This study collected data of patients with advanced cancers and malignant ascites who treated in the Cancer Center of Shanghai Tenth People's Hospital, Tongji University School of Medicine, from January 2019 to January 2023. We excluded patients who did not meet the inclusion criteria. Short-term efficacy was assessed by changes in ascitic fluid volume, and long-term survival was analyzed using the Kaplan-Meier method. The correlation between CA12-5 levels before and after treatment was evaluated using Pearson correlation analysis. Baseline characteristics and treatment outcomes were described using descriptive statistics, and the changes in CA12-5 levels before and after treatment were compared using significance tests (P<0.01). Data entry and statistical analyses were conducted using SPSS version 26.0, and survival curves and efficacy plots were generated with GraphPad Prism (10.4.0 version). The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital (Ethics approval number: SHSY-IEC-5.0/24K134/P01). This prospective single-arm study strictly adhered to the guideline of Consolidated Standards of Reporting Trials (CONSORT) checklist. Results: A total of 21 patients were enrolled in this study. The median age of the patients was 61 years (ranging from 31 to 71 years). Among the 21 patients, 5 (23.8%) achieved complete remission (CR), 5 (23.8%) achieved partial remission (PR), 8 (38.1%) had stable disease (SD), and 3 (14.3%) experienced disease progression (PD). The overall response rate (ORR) was 47.6%, and the disease control rate (DCR) was 85.7%. Survival analysis revealed a median progression-free survival (PFS) of 12.33 months and a median overall survival (OS) of 16.37 months. Analysis of tumor markers showed a significant negative correlation between efficacy and CA12-5 levels (P<0.01). Adverse reactions primarily included myelosuppression, hepatic and renal impairment, and nausea and vomiting, with most adverse events being mild to moderate. Conclusion: Lobaplatin-based HIPEC is effective in the treatment of advanced gastrointestinal malignancies with malignant ascites, providing survival benefits and demonstrating good safety. CA12-5 may serve as a valuable predictor of poor prognosis.