Objective：To investigate the clinical effect and safety of paclitaxel peritoneal perfusion combined with systemic chemotherapy in the treatment of advanced gastric cancer with malignant peritoneal effusion. Methods：A total of 60 patients with ad－vanced gastric cancer and malignant ascites were randomly divided into paclitaxel group and cisplatin group，with 30 patients in each group. The patients were given peritoneal perfusion with paclitaxel or cisplatin after peritoneal effusion drainage. Three times of per－fusion was one course of treatment，and the clinical effect was evaluated after two courses. All patients were given systemic chemother－apy with two drugs in addition to peritoneal perfusion，and clinical outcome and safety were evaluated. Results：All patients were avail－able for evaluation. The paclitaxel group had a response rate（RR） of 60.0%，a disease control rate（DCR） of 83.3%，a median time to progress（TTP） of 10 months，and a KPS score of （78.000±13.235） points；the cisplatin group had an RR of 40.0%，a DCR of 73.3%，a median TTP of 7 months，and a KPS score of （71.000±13.222） points. The paclitaxel group tended to have a better clinical out－come than the cisplatin group（Z=-1.245，P=0.213）. There were significant differences between the two groups in the improvements in TTP and KPS after treatment（TTP：χ2=15.864，P=0.000；KPS：Z=-2.067，P=0.039）. Major adverse reactions included bone marrow suppression，nausea and vomiting，abdominal pain，diarrhea，muscle joint pain，and oral mucositis，and the symptoms were mild and were alleviated after symptomatic treatment，which did not affect the treatment. No allergic reaction or marked liver/renal dysfunction was observed，and there were no treatment-related deaths（P>0.05）. Conclusion：Paclitaxel peritoneal per－fusion chemotherapy has a better clinical effect than cisplatin in the treatment of advanced gastric cancer with malignant peritoneal effusion，with fewer toxicities and side effects. Such treatment has good tolerability in patients and can improve quality of life and prolong TTP.