Objective To explore the risk factors of pleural effusion after cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian cancer. Methods To analyze the clinical data of primary or recurrent ovarian cancer who received CRS+HIPEC in the ovarian cancer database of Beijing Shijitan Hospital. Postoperative patients with pleural effusion were included in the pleural effusion group, and the rest in the non⁃pleural effusion group. We used univariate and multivariate Logistics regression to analyze the data. Results A total of 106 patients were included in this study, with an average age of (56.08± 9.96) years. The incidence of postoperative pleural effusion was 51.89% (56/106), of which bilateral pleural effusion accounted for 63.64% (35/55), left pleural effusion accounted for 25.45% (14/55), and right pleural effusion accounted for 10.91% (6/55). Univariate analysis showed that initial/recurrence, operative time, intraoperative fluid volume, glutamic⁃pyruvic transaminase, diaphragmatic involvement, ascites and hypoalbuminemia had statistical significance (P<0.05). The results of multivariate logistic regression analysis showed that right diaphragmatic involvement (OR=5.66, 95%CI：1.10-29.39), ascites (OR=4.21, 95%CI：1.05-16.83), and recurrence (OR=4.66, 95%CI：1.32-16.42) were independent risk factors for postoperative pleural effusion. Conclusion Patients with right diaphragmatic involvement, ascites and recurrence are independent risk factors for pleural effusion after CRS+HIPEC for ovarian cancer. Postoperative attention should be paid to patients with recurrent ovarian cancer, especially those with involvement of the right diaphragm, and timely drainage of ascites to prevent the occurrence and development of pleural effusion.