Background and Aims: The clinical application of addition of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of gastric cancer is becoming increasingly popular. However, there is still no unified standard for HIPEC in the treatment of gastric cancer, and its safety and efficacy are still unclear. Therefore, the purpose of this study was to investigate the safety and short-term efficacy of radical operation plus intraoperative HIPEC with raltitrexed for locally advanced gastric cancer. 
Methods: By querying the cloud database of gastric cancer of the Department of Oncological Surgery, Anqing Hospital Affiliated to Anhui Medical University, the clinical data of 155 patients with locally advanced gastric cancer who underwent D2 radical gastrectomy from December 2017 to December 2019 were analyzed retrospectively. Of the patients, 52 cases underwent operation plus HIPEC (observation group) and 103 cases underwent operation alone (control group). The postoperative data, postoperative complications and hematological adverse events were compared between the two groups by using the propensity score matching (PSM) to balance the covariates. 
Results: Before the PSM matching, there were significant differences in tumor location and pathological TNM stages between observation group and control group (both P<0.05), and the baseline data of the patients in the two groups were unbalanced. After 1:1 PSM, 100 patients (50 patients in observation group and 50 patients in control group) were matched successfully. There was no significant difference in clinical and pathological staging between observation group and control group (all P>0.05), and the baseline data were well balanced. The operative time before and after matching in observation group were longer than those in control group (both P<0.001). On the first day after operation, the levels of aspartate aminotransferase (AST) and albumin (ALB) in observation group were significantly lower than those in control group before matching (both P<0.05), but there were no significant differences in all laboratory indexes between the two groups on the first day after operation after matching (all P>0.05). There were no significant differences in intraoperative blood loss, time to postoperative first flatus, length of postoperative hospital stay and postoperative pain score in the first three days between the two groups before and after matching (all P>0.05). There were no significant differences in perioperative mortality, unplanned reoperation rate, incidence of postoperative complications, Clavien-Dindo classification of postoperative complications and incidence of hematological adverse events between the two groups (all P>0.05).  
Conclusion: Immediate HIPEC with raltitrexed during radical operation for locally advanced gastric cancer prolongs the time of surgical anesthesia, but it does not affect the postoperative recovery and increase the incidence of postoperative complications. It is safe and reliable, and the long-term effect needs further study, which may bring survival benefits to the patients.