Introduction: Ovarian cancer presents a significant challenge in oncology due to its high mortality rates primarily stemming from late-stage diagnoses. Early detection through reliable biomarkers such as CA-125 and IL-6 is crucial for improving patient outcomes. Aim of the study: This study aimed to compare the accuracy, sensitivity, specificity, and predictive values of CA-125 and IL-6 in detecting malignant ovarian tumors. Methods: A cross-sectional analytical study was conducted at the Department of Gynecological Oncology, BSMMU, and NICRH, Dhaka, Bangladesh. A total of 94 women with suspected ovarian tumors underwent preoperative assessment of CA-125 and IL-6 levels. Receiver-operator characteristic (ROC) curves were utilized to determine optimal cut-off values. Result: In this study of 94 women with ovarian tumors, we evaluated the diagnostic performance of CA-125 and IL-6 biomarkers. CA-125 showed a sensitivity of 83.0% and specificity of 51.2% at a cut-off of ≥89.0 u/ml, while IL-6 exhibited 84.9% sensitivity and 80.5% specificity at ≥9.5 pg/ml. Combining CA-125 and IL-6 improved specificity to 95.1%, maintaining a sensitivity of 77.4%. These findings underscore the potential of biomarker combinations in enhancing diagnostic accuracy for detecting malignant ovarian tumors. Conclusion: IL-6 exhibited higher sensitivity and specificity compared to CA-125 in detecting malignant ovarian tumors. The combined use of both biomarkers improved specificity while maintaining reasonable sensitivity, suggesting their potential utility in clinical practice for early detection and management of ovarian malignancies.