Objective: To analyze the value of human leukocyte antigen-E(sHLA-E) in the diagnosis and prognosis evaluation of endometrial cancer. Methods: 82 endometrial cancer patients who were treated in the hospital from June 2016 to June 2019 were selected as the endometrial cancer group. 80 patients with benign uterine lesions in the same period were aelected as benign uterine lesions group. Another 60 healthy people in the same period were selected as health groups. The clinical data of subjects in three groups were analyzed.Results: The levels of serum CA125, HE4, and sHLA-E of the three groups were significant (F=290.928, P<0.001; F=382.416, P<0.001; F=52.673, P<0.001), the endometrial cancer group was higher than the uterine benign lesions group and the healthy group, and the uterine benign lesions group was higher than the healthy group, showing an upward trend with the severity of the disease (P<0.05); The sHLA-E level of patients with clinical stage Ⅲ and Ⅳ was higher than that of Ⅰ and Ⅱ, the difference was significant (t=2.399, P=0.019); After 18 months of follow-up, the sHLA-E level of patients with recurrence of endometrial cancer was significantly higher than that of patients without recurrence, the difference was significant (t=2.088, P=0.040). The results of Pearson correlation analysis showed that serum sHLA-E levels in patients with endometrial cancer were positively correlated with CA125 and HE4 (r=0.513, P<0.05; r=0.539, P<0.05). ROC curve analysis results showed that the AUC of serum sHLA-E level in the diagnosis of endometrial cancer was 0.823 (95% CI 0.755-0.878, P<0.01), the sensitivity was 73.17% and the specificity was 78.75%.Conclusion: The serum sHLA-E level of patients with endometrial cancer is significantly higher than that of normal people and patients with benign uterine lesions, and as the severity of the disease and the clinical stage show an upward trend, the detection of serum sHLA-E level can help the diagnosis, treatment and prognosis evaluation of patients with endometrial cancer.