Members of the interferon regulatory factor (IRF) gene family are crucial regulators of type I interferon signaling, which may play a role in the resistance of glioma to immune checkpoint blockade. However, the expression profiles, potential functions, and clinical significance of IRF family members remain largely unknown. Here, we examined IRF transcript levels and clinicopathological data from glioma patients using several bioinformatic databases, including ONCOMINE, GEPIA, TCGA, and cBioPortal. We found that IRF1, IRF2, IRF5, IRF8 and IRF9 were significantly upregulated in glioma compared to normal brain tissue. Higher IRF1, IRF2, IRF3, IRF4, IRF5, IRF7, IRF8 and IRF9 mRNA levels correlated with more advanced tumor grades and poorer outcomes. Moreover, although IRFs mutation rates were low (ranging from 0.5% to 2.3%) in glioma patients, genetic alterations in IRFs were associated with more favorable patient survival. Functional analysis showed that IRFs participated in glioma pathology mainly through multiple inflammation- and immunity-related pathways. Additionally, correlations were identified between IRFs and infiltration of immune cells within glioma tissues. Collectively, these results indicate that IRF family members, including IRF1, IRF2, IRF5, IRF8 and IRF9, may serve as prognostic biomarkers and indicators of immune status in glioma patients.