Abstract: Objective To analyze diagnostic value of Copenhagen Index based on pretreatment serum CA125, HE4 and age in differentiating benign and malignant epithelial ovarian tumors. Methods The clinical data were analyzed for 208 consecutive patients with epithelial ovarian tumors (including 100 with malignant and 108 with benign tumors) treated in our department between September, 2014 and September, 2016. The receiver-operating characteristic curve was drawn based on the golden standard of pathological diagnosis for calculation of the diagnostic sensitivity and specificity of CA125, HE4 and the Copenhagen Index. Results In the overall cases, early stage cases and advanced stage cases, the prediction probabilities of CA125, HE4 and Copenhagen Index were all significantly higher for malignant than in benign tumors (P<0.001). The sensitivities of CA125, HE4, Copenhagen Index for differentiating benign and malignant tumors were 81.0%, 86.0% and 91.0% in the overall cases, 64.0%, 68.0% and 72.0% in early stage cases, and 86.7%, 92.0% and 97.3% in advanced stage cases, and their diagnostic specificities were 88.0%, 93.5% and 96.3%, respectively. Copenhagen Index had the highest diagnostic sensitivity (but not in early stage cases) and specificity followed by HE4 and then by CA125 (P<0.001) (P>0.05). Conclusion Copenhagen Index combined with CA125, HE4 and age hase better diagnostic value than HE4 or CA125 alone for differentiation between benign and malignant epithelial ovarian tumors, and can be used clinically to improve the early diagnostic rate of epithelial ovarian cancer.