Objective To investigate the diagnostic value of serum HE4 in patients with ovarian cancer by ECLIA and CMIA. Methods The serum from 39 ovarian cancer patients, 63 benign ovarian diseases patients and 50 healthy individuals were collected. The serum HE4 levels was detected by ECLIA and CMI, and the diagnostic value were evaluated by the two methods. Results The serum level of HE4 was positively correlated between ECLIA and CMIA (r=0.997，P<0.01). There were significant differences in serum HE4 between ovarian cancer patients and ovarian diseases patients or healthy individuals when detected by the same method. When used ovarian diseases patients as control, the area under the ROC curve were 0.813 (ECLIA) and 0.782 (CMIA). Both ECLIA and CMIA had good specificity and accuracy. Conclusion The levels of HE4 detected by ECLIA and CMIA are consistent, and both methods could be used for HE4 detection in the diagnosis of ovarian cancer.