Uterine Corpus Endometrioid Carcinoma (UCEC) is one of the malignant tumors with high incidence of female reproductive system. Despite significant progress in molecular biology research and treatment of UCEC, the molecular mechanisms of UCEC tumorigenesis have not been fully elucidated. The purpose of this research was to identify differentially expressed genes (DEGs) association with the pathogenesis of UCEC, and to further define available prognostic biomarkers and immunotherapy targets for UCEC. RNA expression datasets and clinical data for UCEC patients were collected from the UCSC Xena database and The Cancer Genome Atlas (TCGA) database. 174 UCEC tissues and 23 normal endometrial tissues were screened using PCA and LIMMA methods. Analysis of GO enrichment indicated that the up-regulated DEGs were mainly involved in tissue development, cell cycle regulation and epithelial development. Subsequently, DEGs was identified by weighted gene co-expression network analysis (WGCNA). DEGs in blue modules were determined to be significantly positively correlated with UCEC, conversely, black modules were significantly negatively correlated with UCEC. Finally, 16 genes were identified by WGCNA, and further Kaplan-Meier (KM) analysis revealed that 5 of the 16 genes were significantly negatively correlated with overall survival (OS) namely hub genes, including AURKA, CCNE1, IQGAP3, TTK and UBE2C. Further, the expression of hub gene was verified by GEO dataset and IHC analysis in the Human Protein Atlas. Finally, potential immunotherapeutic targets and approaches were revealed by calculating immune scores for immune infiltration, immune cell infiltration, and immune cell regulator across the 5 hub genes. In conclusion, In conclusion, this study probed into the molecular mechanisms of UCEC development in depth, and identifies 5 promising prognostic biomarkers and immunotherapy targets in UCEC progression, providing directions for the treatment of UCEC.