Abstract：Objective To evaluate the value of human epididymis secretory protein 4 (HE4) in the diagnosis of epithelial ovarian malignancy. Methods The serum HE4 and CA125 levels in 54 patients with epithelial ovarian cancer, 60 cases of benign ovarian diseases and 60 healthy women were detected. The serum levels and the diagnosis efficiency of the HE4 and CA125 were analyzed. Results The median levels of HE4 and CA125 were significantly higher in epithelial ovarian cancer group (142.72 pmol/L and 136.07ku/L respectively) than those of the benign ovarian diseases group (63.72pmol/L and 70.20ku/L respectively) and healthy women group (57.82pmol/L and 57.42ku/L respectively)(P<0.01). The operating characteristic-area under the curve (ROC-AUC) of HE4 and CA125 assay were 0.958 and 0.886 respectively, there was statistically difference between them (P<0.001). Conclusion The specificity of HE4 assay has advantage over CA 125 in the diagnosis of epithelial ovarian malignancy.