Objective To evaluate the value of serum human epididymal secretory protein 4(HE4), carbohydrate antigen 125(CA-125)and the risk of ovarian malignancy algorithm(ROMA)index in the diagnosis of pelvic malignant tumor. Methods HE4,CA-125 level and ROMA index of sera in patients with ovarian cancer, endometrial cancer, cervical cancer, ovarian benign tumor, uterine benign disease and healthy control were detected by electrochemiluminescence immunoassay. Results Serum HE4 levels in both ovarian cancer group and endometrial cancer group were significantly higher than that of other groups(P<0.01). Serum CA-125 level in ovarian cancer group was significantly higher than that of other groups except for endometrial cancer group(P <0.01). Serum CA-125 levels in ovarian benign tumor group and uterine benign disease group were significantly higher than that of healthy control group(P<0.05). With ovarian benign tumor group as a reference to ovarian cancer, both the specificity and positive predictive value of HE4 in premenopausal ovarian cancer group reached up to 100%, and the accuracy was 93.9%, which were significantly higher than that of CA-125 and ROMA(P<0.01). Of three indicators, CA-125 had the highest sensitivity of 88.9%, which significantly higher than that of HE4(P<0.05). However, in post menopause ovarian cancer group, there was no significant difference existed on the specificity, sensitivity and accuracy of three indicators(P>0.05). Regardless of menopause,in three indicators, specificity, positive predictive value and accuracy of HE4 were highest(98.1%, 91.7% and 91.4%)in three indicators, and sensitivity and negative predictive value(81.3% and 93.6%)of ROMA index were highest. With ovarian benign tumor group and healthy control group as a reference to ovarian cancer, the area under ROC curve of HE4, CA-125 and ROMA index was 0.919, 0.814 and 0.921 respectively. With uterine benign disease group as a reference to endometrial cancer, the specificity, positive predictive value and accuracy of HE4 alone were significantly higher than that of CA-125 alone(P<0.05),HE4 and CA-125 combined detection of endometrial cancer sensitivity were higher than single detection. With uterine benign disease group and healthy control group as a reference to endometrial cancer, the area under ROC curve of HE4 and CA-125 was 0.916, 0.731. Conclusion Serum HE4 may be as an important indicator in the diagnosis of ovarian cancer and endometrial cancer, with higher spectivity and accuracy than CA-125, Combining CA-125 could improve the diagnosis of endometrial cancer. ROMA index may be a valuable index contributed to improving the diagnostic efficiency of ovarian cancer greatly.