Abstract： Objective To investigate the value of human epididymis secretory protein 4 ( HE4 ) combined with CA125 assay in differential diagnosis of endometriosis cyst and ovarian malignant tumor.Methods The level of HE4 and CA125 were measured by enzyme-linked immunosorbent assay (ELISA) in the serum specimens of 46 cases in endometriosis cyst group,36 cases in malignant ovarian tumor group,60 cases in benign ovarian diseases and 50 women in healthy women group.Those results were shown with median level.The normal range were 0-150 pmol/L in HE4 and 0-35 kU/L,which either one was more than the threshold value defined as positive index.The sensitivity of assay was evaluated by receiver operating characteristic (ROC) curve,the relation and value of HE4 or CA125 alone and combination assay in diagnosis of endometriosis was analyzed by Mann-Whitney U test and correlation analysis.Results (1) HE4:the median levels of HE4 were 52.4,51.0,50.0 pmol/L in group of endometriosis,normal control and benign ovarian tumor,which didn't show statistical difference.However,HE4 was 507.5 pmol/L inovarian cancer group,which was significantly higher than those of 3 groups (P < 0.05 ).(2 ) CA125:there were significant different in median level of CA125 was observed as 743.0 kU/L in ovarian cancer,84.9 kU/L in endoemtriosis,15.4 kU/L in benign ovarian disease,and 11.5 kU/L in healthy women (P < 0.05).( 3 ) The single assay:when compared with that in endometriosis group,receiver operating characteristic area under the curve( ROC-AUC) were 0.933 in HE4 alone and 0.821 in CA125 alone assay in ovarian cancer group.The specificity was 95% and the sensitivity was 79.6% and 49.0%.(4) The combination assay:when compared with those in endometriosis group,the ROC-AUC was 0.936,the specificity was 95% and the sensitivity was 81.0% in ovarian cancer.Conclusions Measurement of HE4 could be used in differential diagnosis of endometriosis cyst.And the combination of HE4 and CA125 assay could discriminate ovarian endometriosis cysts from ovarian malignant tumors effectively.