Objective：This study aims to evaluate the predictive value of serum HE4，CA125 and ROMA（Risk of Ovarian Malignancy Algorithm）in the diagnosis of ovarian malignancies. Methods：This research enrolled 370 patients with benign or malignant gynecological tumors treated in the First Affiliated Hospital of Nanjing Medical University. Serum levels of HE4 and CA125 were measured by electrochemiluminescence. The predicted probability of ovarian malignancy（PP） was calculated by ROMA method in 194 patients initially diagnosed as pelvic mass. The sensitivity，specificity，positive predictive value and negative predictive value of each indicators in diagnosing ovarian malignancy were calculated and the ROC curves were drawn. Results：The level of serum HE4 in ovarian malignancy group was significantly higher than that in other benign or malignant gynecological tumors groups（P < 0.05）. The level of serum CA125 in ovarian malignancy group was significantly higher than that in other groups except ovarian borderline tumors group and uterine adenomyosis group（P < 0.05）. The level of serum HE4 in patients with epithelial ovarian cancer（EOC）was significantly higher than that in patients without EOC（P < 0.05）. The levels of serum HE4 and CA125 in EOC patients with positive ascites were significantly higher than those in patients with negative ascites（P=0.001，P < 0.001）. The level of serum HE4 in EOC patients with abnormal D-dimer were significantly higher than those in patients with normal D-dimer（P=0.038）. The sensitivity of CA125 was significantly higher than that of HE4（P=0.031）. The positive predictive value of HE4 was significantly higher than that of ROMA or CA125（P < 0.05）. The ROC-AUC of ROMA was higher than that of CA125（P=0.006）. Conclusion：The specificity of serum HE4 was higher than that of CA125 in the diagnosis of ovarian malignancies. The combined ROMA index had better predictive value than detecting CA125 alone.