OBJECTIVE: To study the characteristics of HE4 expression in patients with epithelial ovarian cancer, and to evaluate whether the pre-treatment serum human epididymis protein 4 (HE4) level is an independent prognostic factor in the patients. METHODS: The clinicopathological characteristics and follow-up information of 112 patients with epithelial ovarian cancer were collected. The pre-treatment serum samples from these patients were measured for HE4 and CA125 expression. Serum HE4 levels were tested by a quantitative enzyme-linked immunosorbent assay (ELISA) and serum CA125 levels were tested using Elecsys kit. The correlation of HE4 and CA125 expressions with overall survival and other clinical data were analyzed. RESULTS: The median level of pre-treatment serum HE4 and CA125 in the 112 patients was 415.5 pmol/L (26.9-3253.5 pmol/L) and 699 U/ml (5-17 694 U/ml), respectively. Serum HE4 level before treatment was significantly related to grade (r = 0.21, P = 0.037), stage (r = 0.40, P = 0.001), amount of ascites (r = 0.39, P = 0.001), serum CA125 level (r = 0.53, P = 0.001) and residual disease after surgery (r = 0.22, P = 0.027), but was not related to menopausal stauts (P = 0.115), revealed by Spearman correlation test.However, logistic multivariate regression analysis indicated that residual tumor size was not significantly correlated with pre-operative HE4 level (P = 0.259). The mean survival of the 112 patients was 53 months. Log rank test indicated that the overall survival in patients with higher HE4 level was significantly shorter than those with lower HE4 level (P = 0.001). Multivariate Cox proportional hazard model analysis revealed that the pre-treatment serum HE4 level and residual tumor size were independent prognostic factors for overall survival (P = 0.044 and P = 0.048). CONCLUSION: Pre-treatment serum HE4 level is a valuable prognostic factor for the overall survival in patients with epithelial ovarian cancer.