Abstract:〔Abstract〕 Objective To investigate the expression and significance of serum adiponectin (APN), osteopontin (OPN) and human epididymis secreted protein 4 (HE4) in patients with endometrial cancer. Methods A total of 62 patients with endometrial cancer (endometrial cancer group), 50 patients with endometrial dysplasia (endometrial hyperplasia group) and 50 healthy volunteers (normal endometrial group) were selected from Chenzhou First People's Hospital from November 2019 to September 2022. Serum levels of APN, OPN, HE4 were detected and compared among the three groups. The diagnostic efficacy of serum APN, OPN, HE4 in endometrial cancer was analyzed by receiver operating characteristic (ROC) curve, and the correlation between serum APN, OPN, HE4 and clinicopathologic features was analyzed by Spearman correlation analysis. Results The serum levels of APN in endometrial carcinoma group were lower than those in endometrial hyperplasia group and normal endometrial group, while the levels of OPN and HE4 were higher than those in endometrial hyperplasia group and normal endometrial group. FIGO staging showed that the level of serum APN in stage Ⅲ patients was lower than those in stage Ⅱ and stage Ⅰ patients, and the levels of OPN and HE4 was higher than those in stage Ⅱ and stage Ⅰ patients. The APN level in patients with ≥ 1/2 muscle layer infiltration depth was lower than that in < 1/2 muscle layer, and the OPN and HE4 levels were higher than those in < 1/2 muscle layer. The serum APN level in patients with lymph node metastasis was lower than that in patients without lymph node metastasis, and the levels of OPN and HE4 were higher than those in patients without lymph node metastasis, with statistical significance (P < 0.05). ROC curve analysis showed that the area under the curve of serum APN, OPN and HE4 combined detection was 0.936, the sensitivity was 91.7 %, and the specificity was 88.1%, all of them were higher than those of serum APN, OPN and HE4 alone. Spearman correlation analysis showed that serum APN was negatively correlated with FIGO stage, depth of muscle infiltration and lymph node metastasis. Serum OPN and HE4 were positively correlated with FIGO stage, depth of muscle infiltration and lymph node metastasis. Conclusion Serum APN, OPN, HE4 play an important role in the occurrence and development of endometrial cancer. The expressions of APN, OPN, and HE4 are significantly correlated with the clinical staging of endometrial cancer, the depth of muscle infiltration, and lymph node metastasis, and the combined detection can improve the diagnostic efficiency of endometrial cancer.