Purpose: It is reported that Cullin 4B (CUL4B) plays a crucial role in many physiological process. This study for the first time investigated the role of CUL4B in endometrioid adenocarcinoma (EAC). Materials and Methods: CUL4B mRNA and protein expression in EAC tissues and normal endometrial (NE) tissues were examined by real-time PCR and immunohistochemistry. The authors also explored the correlation between CUL4B protein expression and clinicopathological characteristics. Moreover, univariate and multivariate Cox regression analyses and Kaplan-Meier survival analyses were performed to investigate the association between TRIM62 expression and EAC patients’ prognosis. Results: CUL4B was markedly overexpressed in EAC at both mRNA and protein levels. Immunohistochemistry assays showed that high CUL4B expression was significantly correlated with FIGO stage (p = 0.008) and histological grade (p = 0.002). Univariate and multivariate analyses revealed that CUL4B was an independent poor prognostic factor for overall and disease-free survival of EAC patients (p < 0.05). Furthermore, survival analyses displayed that patients with high CUL4B expression had poor prognosis. Conclusion: The present results demonstrated that elevated CUL4B was associated with poor outcomes of patients with EAC. CUL4B may serve as a novel prognostic marker and therapeutic target for EAC.