Abstract: Objective To investigate the differential significance of red blood cell distribution width (RDW), mean platelet volume (MPV) and cancer antigen 125 (CA125) in the diagnosis of benign and malignant ovarian tumors. Methods A total of 607 patients with pelvic masses admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to January 2019 were enrolled, including 268 patients with ovarian cancer and 339 patients with benign ovarian tumors. The selected subjects were diagnosed by pathology. A total of 200 healthy subjects in the same period were selected as the control group. The clinical biochemical parameters, RDW and MPV levels of the three groups were retrospectively analyzed. The correlation between preoperative RDW and MPV and clinicopathological features in patients with ovarian cancer was investigated. The sensitivity and specificity of patients with ovarian cancer and benign ovarian tumors were identified. Results The RDW (%) of ovarian cancer group, ovarian benign tumor group and control group were 13.86±1.22, 12.82±0.83 and 11.91±0.99, respectively. The difference between the two groups was statistically significant (P<0.001); MPV(fl) was 9.29±1.36, 10.89±0.94 and 12.26±1.55, the difference between the two groups was statistically significant (P<0.001). The sensitivity, specificity and AUC of RDW, MPV and CA125 combined detection for ovarian cancer and ovarian benign tumor were 93.0%, 85.0% and 0.931 (0.907-0.955), respectively. Conclusion The combination of red blood cell distribution width, mean platelet volume and cancer antigen 125 can effectively identify ovarian cancer and benign ovarian tumors clinically