Objective To study the association of DIRAS3 with the prognosis of patients with glioma and the potential mechanisms.Methods Using DIRAS3 expression profiles and clinical data extracted from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas databases， we studied DIRAS3 mRNA expression levels in patients with glioma with different clinicopathological features as well as its relationship with overall survival and clinicopathological features. Subsequently， we collected 32 normal brain and glioma tissue specimens to compare DIRAS3 protein expression levels in different grades of gliomas and normal tissues by Western blot and immunohistochemistry. Through Gene Ontology analysis， Kyoto Encyclopedia of Genes and Genomes analysis， gene set enrichment analysis， and gene set variation analysis， we explored the possible biological functions and signaling pathways of the DIRAS3 gene and its co-expressed genes. We also explored the relationship between DIRAS3 and the degree of immune cell infiltration and the expression of immune-related molecules.Results DIRAS3 was significantly overexpressed in gliomas. The expression level of DIRAS3 increased with the increase in the World Health Organization classification of gliomas， and was negatively correlated with the overall survival rate of patients. The bioinformatics analysis showed that the high expression of DIRAS3 was associated with patient’s age， tumor grade， isocitrate dehydrogenase mutation status， and 1p/19q deletion. In addition， DIRAS3-associated co-expressed genes were enriched in various immune-related pathways to play a regulatory role in a variety of processes in immune response.Conclusions DIRAS3 is not only a diagnostic and prognostic biomarker for gliomas， but also a key target for glioma immunotherapy.