Objective To investigate the role of aberrant expression of PTEN, HIF-1α and NDRG1 protein in the pathogenesis and progression of endometrioid carcinoma. Methods Tissue microarray and immunohistochemical staining were employed to detect the expression of PTEN, HIF-1α and NDRG1 in tissues of type I endometrial carcinoma (n=124) and atypical hyperplasia (n=28) and normal endometrial tissues (n=35). The relationship among the markers, as well as their correlations with clinicopathological features were evaluated. Results The expression of PTEN, HIF-1α and NDRG1 in tissues of endometrioid carcinoma was 29.8%, 61.3% and 52.4%, respectively, and was significantly different from that in tissues of atypical hyperplasia and normal endometrial tissues (P<0.01). The downregulation of expression of PTEN and overexpression of NDRG1 were significantly related to the tumor differentiation (P<0.05), and the expression of HIF-1α protein was significantly related to the tumor differentiation, myometrial invasion and lymph node metastasis (P<0.05). The expression of PTEN was negatively related to that of HIF-1α and NDRG1 in tissues of endometrioid carcinoma (r=-0.314, P<0.01, r=-0.296, P=0.001), and the expression of HIF-1α protein was positively related to that of NDRG1 (r=0.237, P=0.008). Conclusion The absence of PTEN may upregulate the expression of HIF-1α and NDRG1 protein, which may be involved in the pathogenesis and progression of endometrioid carcinoma, and the combined detection of these markers is of great value in the prediction of tumor behavior and prognosis.