Abstract: Objective To explore the value of combined detection of human protein DJ-1, human epididymal protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the diagnosis of endometrial carcinoma.Methods The serum samples were collected from 39 patients with endometrial carcinoma (an endometrial carcinoma group), 39 patients with uterine leiomyoma (a benign group) and 38 healthy individuals (a healthy group). The levels of DJ-1, HE4 and CA125 were measured in these samples. The receiver operating characteristic (ROC) curve and the area under ROC curve (AUC) were used to analyze the role of DJ-1, HE4, CA125 and their combination in the diagnosis of endometrial carcinoma.Results The levels of HE4 and CA125 significantly increased in the serum of endometrial carcinoma group compared with the healthy group and the benign group, while the levels of DJ-1 significantly decreased(P＜0.05). There was no statistical significance in CA125 between the healthy group and the benign group (P＞0.05). However, the differences in DJ-1 and HE4 between any two groups were statistically significant (P<0.05). The expression of serum HE4 in patients with endometrial carcinoma was related to lymph node metastasis and FIGO stage, and the expression of serum CA125 and HE4 was related to myometrial invasion (P＜0.05). The AUC for DJ-1, HE4 and CA125 and their combination were 0.776, 0.917, 0.741, and 0.953, respectively, with the highest AUC observed from the combination of the three markers. The sensitivity of DJ-1, HE4 and CA125 in diagnosing endometrial cancer was 76.92%, 69.23%, and 71.79%, respectively, and the specificity was 76.32%, 100%, and 71.05%, respectively, while the sensitivity and specificity of the combined detection were 92.31% and 86.84%, respectively.Conclusions Combined detection of DJ-1, HE4, and CA125 is more effective for diagnosing endometrial carcinoma than each marker alone, which can provide valuable reference for the comprehensive clinical diagnosis of endometrial cancer.