Objective To investigate the expression of erythropoietin-producing human hepatocellular receptors B4(EphB4)and its upstream targets as well as correlation with prognosis in low-grade glioma(LGG),for analyzing its potential role as a therapeutic tar-get.Methods Firstly analyzed the expression of EphB4 in glioma and normal brain tissue by The Cancer Genome Atlas(TCGA)data-base.Then,Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the effects of EphB4 on various cancer survival.The possible upstream regulatory non-coding RNA(ncRNA)of EphB4 were analyzed by R and starBase database.The correla-tion of EphB4 with tumor immune cell infiltration,biomarkers of immune cells and immune checkpoint expression were analyzed using the Tumor Immune Estimation Resource(TIMER)database.Results UBA6-AS1/hsa-miR-346 axis was the most potential upstream non-coding RNA(ncRNA)related pathway to influence expression of EphB4 in LGG.At the same time,the level of EphB4 was posi-tively correlated with the tumor immune cell infiltration,immune cell biomarkers and immune checkpoint in LGG.Conclusion NcRNA-mediated up-regulation of EphB4 is associated with poor prognosis and tumor immunoinfiltration in LGG.