Objective: This retrospective study aimed to investigate the predictive role of the systemic immune-inflammatory index (SII) in distinguishing between benign and malignant adnexal masses in women. Methods: A total of 268 female patients with adnexal masses who underwent surgical intervention were included. Patient data, including complete blood count and cancer antigen 125 (CA125) levels, were collected, and final pathological examinations were assessed. Patients with prior cancer diagnoses, non-epithelial ovarian cancer, and inflammatory, hematologic, or autoimmune diseases were excluded. Results: The study included 177 women with benign and 91 women with malignant ovarian tumors. SII and CA125 showed significant differences between the two groups, with both markers found to be significantly higher in the malign group (p160) and elevated SII (>5.63) were associated with increased risks of having a malignant tumor (p