Diffuse gliomas are the most prevalent primary brain tumors. The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases provide evidence of the relationships between gliomas and altered molecular pathways. In glioma pathogenesis, the microenvironment has emerged as a potential indicator of tumor progression.We investigated and confirmed the role of RELT-like 1 (RELL1) oncogene in glioblastoma and low-grade glioma by data mining large cohorts of TCGA and the CGGA. Correlations between immune cells and RELL1 were verified using the CIBERSORT algorithm.Our analysis revealed that RELL1 expression was much higher in grade-dependent glioma patients with poor prognosis. Comparable prognostic values for isocitrate dehydrogenase 1 (IDH1) and RELL1 were observed during in-depth analyses of the integrated correlations. Moreover, RELL1 was found to be associated with numerous tumor-infiltrating immune cells in glioma-affected patients.We conclude that RELL1 might serve as a potential therapeutic target or prognostic marker in glioblastoma and diffuse glioma cases.