Objectives: To assess circulating cell-free DNA's diagnostic potential in Egyptian women with ovarian cancer. Background: Ovarian cancer (OC), one of the most common cancers worldwide, is the most lethal form of gynecological cancer, but the early detection of ovarian cancer would significantly decrease its mortality rate. Circulating plasma cell-free DNA (cfDNA) is nucleic acids in peripheral blood that originate from cell death caused by injury, apoptosis, and necrosis. Circulating cfDNA is normally found in small amounts in the blood of healthy individuals, although increased cfDNA levels have been reported in patients with various clinical conditions, including infection, inflammation, malignancy, connective tissue diseases, ischemic stroke, myocardial infarction, pregnancy-associated disorders, and hemodialysis. Subjects and Methods: This study was conducted on 50 patients with OC, 25 patients with benign ovary disease (BOD), and 25 healthy women used as a control group. All participants were tested for AFP, HCG, CA125, LDH, and circulating cfDNA, which were measured using real-time quantitative Polymerase chain reaction (RT-qPCR). Results: Circulation cfDNA rises more dramatically between OC cases than in both BOD cases and healthy controls, and the results indicate that circulating cfDNA was significantly higher in the OC group (p < 0.001) than both the BOD and control groups. The receiver operator of characteristics (ROC) curve analysis of circulating cfDNA revealed that at a cut-off value of > 4.13 (fold expression), the sensitivity and specificity for differentiation of OC cases from non-cancer subjects were 97.3% and 92%, respectively. A significant positive correlation was found between circulating cfDNA and CA 125.Conclusion: Circulating CfDNA might be a biomarker for the early diagnosis of ovarian cancer.