This study aimed to explore the clinical significance of AAA+ (ATPases associated with various cellular activities) nuclear coregulator cancer-associated (ANCCA) protein expression in endometrial carcinoma (EC). Correlations of ANCCA expression with clinicopathological factors and prognosis of EC patients were analyzed. Expression of ANCCA was detected in EC from 207 patients along with corresponding normal endometrium specimens by immunohistochemistry. ANCCA immunoreactivity was overexpressed in EC cases compared with that in normal endometrium (P < 0.001). High ANCCA expression was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, depth of myometrial invasion, lymph node metastasis, lymph vascular space involvement, and recurrence but not with age and histological type. Patients with high ANCCA expression exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than patients with low ANCCA expression (P = 0.001 and 0.002, respectively). Cox multivariate analysis showed that high ANCCA expression was an independent prognostic factor for both OS (hazard ratio (HR) = 4.954, 95 % confidence interval (CI) = 1.537-15.966; P = 0.007) and DFS of patients with EC (HR = 4.237, 95 % CI = 1.295-13.859; P = 0.017). We identified ANCCA protein expression as a novel independent poor prognostic indicator in EC.