Abstract: Objective To investigate the expression of human epididymal protein 4 (HE4) in ovarian cancer and its relationship with the prognosis and survival of ovarian cancer.Methods A total of 26 ovarian benign tumor patients(group A), 20 ovarian cancer patients(group B), 25 ovarian chocolate cysts(group C), and 25 borderline ovarian tumor patients(group D) who was diagnosed in Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University from January 2015 to July 2017 were enrolled. The level of serum HE4 in each group was detected and the ROC curve was plotted to determine the cutoff values of HE4 in prediction of EOC survival time. The association of age, tumor grade, type, and stage, tumor metastasis and differentiation, and HE4 level with the prognosis of EOC patients was analyzed by Kaplan-Meier method and Log-rank method. Results Group B produced higher levels of HE4 than the other groups(P<0.05). Tumor grade, stage, metastasis and HE4 level were independent risk factors affecting the prognosis of EOC patients(P<0.05). The overall survival(OS) and progression-free survival(PFS) was longer in patients with low expression of HE4 than those with high expression of HE4 (P<0.05). Conclusions HE4 is expressed in different types of ovarian cancer tissues at different levels, which provides evidence for early diagnosis, treatment and prognosis of EOC patients.