Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proven to improve the survival rate of gastric cancer and reduce peritoneal recurrence. We aimed to evaluate the effectiveness and safety of prophylactic HIPEC after radical gastric cancer surgery in this study. Researchers searched for studies published in PubMed, Embase, Web of science, Scopus, Cochrane, Clinical key databases and Microsoft Academic databases to identify studies that examine the impact of prophylactic HIPEC on the survival, recurrence and adverse events of patients undergoing radical gastric cancer surgery. RevMan 5.3 was used to analyze the results and risk of bias. The PROSERO registration number is CRD42021262016. This meta-analysis included 22 studies with a total of 2097 patients, 12 of which are RCTs. The results showed that the 1-, 3- and 5-year overall survival rate was significantly favorable to HIPEC (OR 5.10, 2.07, 1.96 respectively). Compared with the control group, the overall recurrence rate and peritoneal recurrence rate of the HIPEC group were significantly lower (OR 0.41, 0.24 respectively). Significantly favorable to the control group in terms of renal dysfunction and pulmonary dysfunction complications (OR 2.44, 6.03 respectively). Regarding the causes of death due to postoperative recurrence: liver recurrence, lymph node and local recurrence and peritoneal recurrence, the overall effect is not significantly different (OR 0.81, 1.19, 0.37 respectively). 1-, 3- and 5-year overall survival follow-up may be incremented by the prophylactic HIPEC, and which reduce the overall recurrence rate and peritoneal recurrence rate. HIPEC may have high-risk of pulmonary dysfunction and renal dysfunction complications. No difference has been found in the deaths due to recurrence after surgery.© 2022. The Author(s).