Abstract Background: Gliomas, characterized by aggressiveness and invasiveness, remain incurable after conventional therapies. The molecular mechanisms driving the progression and maintenance of glioma are still poorly understood. Methods: PDIA4 expression was analyzed via Gene Expression Profiling Interactive Analysis (GEPIA) which data were from TCGA and GTEx databases. We estimated the prognostic value of PDIA4 using Kaplan–Meier survival analysis and the Cox proportional hazard model. The functional enrichment analysis was done by using cluster Profiler package in R language, including gene ontology (GO) analysis comprised of cellular component (CC), molecular function (MF), and biological process (BP), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. In addition, correlation between PDIA4 and immunity were analyzed by Protein-protein interaction (PPI) analysis, RNA extraction and Real-time RT-PCR. Results: In this study, we identified PDIA4 was highly expressed in gliomas and closely correlated with poor prognosis. The association with IDH1 and different patterns of gliomas also indicates the potential biological processes that PDIA4 involves in the development of tumor. Mechanistically, PDIA4 interacts with multiple immunological components to promote an immunosuppressive tumor microenvironment (TME). Conclusions: Our results confirm PDIA4 is an efficient biomarker of gliomas, with implications for prognosis and therapeutic strategies. Keywords: PDIA4, glioma, prognosis, biomarker, immune cells