〔Abstract〕 Objective To confirm the expression of EPHB2 associated with clinical value and prognosis in endometrial cancer(EC). Methods The role of EPHB2 in ECs was investigated by using publicly available dataset from The Cancer Genome Atlas(TCGA). The correlations between clinical pathologic parameters and EPHB2 were analyzed by the Wilcox test and logistic regression. Then Cox regression and Kaplan-Meier survival analysis were used to analyze the relationships between clinicopathologic characteristics and EPHB2 expression and overall survival in TCGA database. Gene Set Enrichment Analysis(GSEA) was also conducted by TCGA. Results The expression of EPHB2 was increased in EC compared to the normal endometrium. Increased EPHB2 expression in EC was significantly correlated with stage(OR=2.58 for Ⅲ/ⅣvsⅠ/Ⅱ), grade(OR=2.41 for high gradevslow grade), histology type(OR=13.86 for serous/mixed serous endometrioid adenocarcinomavsendometrioid adenocarcinoma) and peritoneal cytology(OR=4.56 for positivevsnegative), etc(P<0.05). Kaplan-Meier methods revealed that patients of EC with high EPHB2 expression had a poor prognosis than those with low EPHB2 expression. The univariate and multivariate analysis showed that EPHB2 could become an independent predictor for poor outcome of EC(P<0.05). GSEA suggested that axon gidance might be enriched in EPHB2 high expression phenotype and α linolenic acid were enriched in EPHB2 low expression phenotype. Conclusion EPHB2 may be associated with development of EC, which could be a potential prognostic molecular marker for poor survival in EC.