OBJECTIVE: To explore the impact of DIRAS3 on the prognosis of glioma patients and its potential causes. METHODS: Based on TCGA and CGGA databases, we performed the extraction of DIRAS3 expression profiles and clinical data. The study analysed the mRNA expression levels of DIRAS3 in glioma patients with different clinicopathological features and investigated its impact on overall survival and clinicopathological features. Subsequently, we collected 32 normal brain and glioma tissue specimens, which were validated to compare the differences in DIRAS3 protein expression in different grades of gliomas and normal tissues. Through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), we provided insights into the possible biological functions and signal transduction pathways of DIRAS3 and its co-expressed genes. Finally, we also explored the relationship between DIRAS3 and the degree of immune cell infiltration and the expression of immune-related molecules. RESULTS: Overexpression of DIRAS3 was evident in gliomas, and its expression level increased with the elevated World Health Organization (WHO) classification and showed a negative correlation with the overall survival of patients. In addition, the high expression of DIRAS3 was associated with patient age, tumour grade, IDH status, and 1p/19q coding deletion.DIRAS3 may influence the infiltration degree of multiple immune cells in the tumour microenvironment by regulating various processes of immune response. CONCLUSION: DIRAS3 is not only a diagnostic and prognostic biomarker for glioma, but also a key target for glioma immunotherapy. Through in-depth study of DIRAS3, we are expected to reveal the pathogenesis of glioma and provide new ideas and methods for its treatment.