Background: This study aimed to analyze the clinical value of the Ovarian-Adnexal Reporting and Data System (O-RADS) classification combined with hematological indices for the diagnosis of benign and malignant ovarian-adnexa. Methods: A retrospective analysis of 153 cases of ovarian adnexal masses was performed. All patients underwent O-RADS classification, and hematological indexes were measured upon admission, including neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), fibrinogen (FIB), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199) and human epididymis protein 4 (HE4). Results: The diagnostic results of O-RADS classification were consistent with the pathological findings in 134 cases, while 19 cases showed discrepancies, yielding an accuracy rate of 87.58%, demonstrating good agreement (Kappa = 0.713, p < 0.001). Compared with the benign group, patients in the malignant group exhibited a significantly higher proportion of tumors >5 cm in size (54.81%), as well as elevated neutrophil count, NLR, FIB, CRP, CA125, HE4 and CA199 levels (p < 0.05). Lymphocyte counts were significantly lower in the malignant group (p < 0.05). Multivariate analysis identified NLR, FIB, CRP, CA125 and HE4 as independent risk factors for ovarian-adnexal tumors (p < 0.05). The area under the curve (AUC) values for diagnosing ovarian-adnexal malignancy were as follows: NLR (0.813), FIB (0.788), CRP (0.780), CA125 (0.816), HE4 (0.771) and CA199 (0.604). The combined assessment of hematological indexes yielded an AUC of 0.844. Notably, the combination of O-RADS classification combined with hematological indexes achieved the highest diagnostic performance, with an AUC of 0.955, significantly higher than that of O-RADS or and hematological indexes alone (p < 0.05). Conclusions: Combining O-RADS classification with hematological indexes significantly enhances the diagnostic accuracy for distinguishing benign from malignant ovarian-adnexal masses. This integrated approach facilitates earlier detection and holds significant potential for clinical application in routine screening and diagnosis.