Since therapeutic strategies are limited in gliomas, new molecules or biomarkers are essential for diagnosis and therapy. Here, we investigated expression of protein disulfide isomerase family A member 3 (PDIA3) in gliomas to evaluate its potential as a promising immune target or biomarker. Transcriptome level, genomic profiles and its association with clinical practice from TCGA and CGGA databases were analyzed. All statistical analyses were performed using R project. In gliomas with high PDIA3 expression, somatic mutations showed the correlation with loss of PTEN and amplification of EGFR; meanwhile, in PDIA3 low gliomas, mutations in isocitrate dehydrogenase (IDH) took 80%. Moreover, PDIA3 was found to positively correlate with ESTIMATE scores and diverse infiltrating immune and stromal cell types localizing in tumor microenvironment. PDIA3 was found to be highly correlated with macrophage and T cells based on single cell sequencing. Additionally, PDIA3 was also involved in suppression of anti-tumor immunity via multiple immune regulatory processes. Finally, PDIA3 was observed to correlate with other immune checkpoint inhibitors and associated with inflammation. Our findings identified the significance of PDIA3 in the process of gliomas and demonstrated the potential of PDIA3 as a molecular target in prognosis and immune related treatment of gliomas