Objective To explore the relationship between poliovirus receptor-related protein 2 （PVRL2） gene expression and prognosis， immune infiltration， and molecular characteristics of gliomas. Methods University of California Santa Cruz（ UCSC） dataset was used to analyze the differences in PVRL2 gene expression， and the genomic and clinical data of 656 glioma（ GBMLGG） patients from The Cancer Genome Atlas（ TCGA） database were integrated to study the relationship between PVRL2 expression and clinical grade. The optimal cutoff value was determined by R package maxstat， and the samples were divided into high- expression group and low-expression group， and survival differences were assessed using Kaplan- Meier survival curves and log-rank tests and analyzed by Cox one-way regression. The correlation between PVRL2 expression and tumor stemness score was analyzed using Pearson correlation. Co-expressed genes， gene ontology（ GO）function and Kyoto encyclopedia of genes and genomes（ KEGG） pathway enrichment were analyzed to construct PPI networks. Correlation with immune cell infiltration and immunomodulatory genes was analyzed. Results PVRL2 was up-regulated in 25 types of tumors， down-regulated in 5 types of tumors， and significantly up-regulated in GBMLGG， with statistically significant differences（ P ＜0.05）. The expression value of PVRL2 was higher in high-grade gliomas（ 4.78±0.72） than in low-grade gliomas （4.41±0.51）， and the difference was statistically significant（ P ＜ 0.001）. The optimal cutoff value was calculated to be 5.190 7， and the patients were divided into high and low expression groups according to the cutoff value. Kaplan-Meier survival analysis showed that the survival of high expression group was shorter than that of low expression group in patients with total gliomas， low-grade， and high-grade gliomas， and the hazard ratios were all greater than 1， and that the PVRL2 expression was positively correlated with the risk of death and disease progression， and the differences were all statistical（ P ＜ 0.05）. PVRL2 was positively correlated with stemness scores based on DNA methylation， differential methylation， epigenetic regulation of DNA methylation and enhancer DNA methylation， with statistically significant differences（ all P ＜ 0.001）. PVRL2 was co-expressed with 20 118 genes， and enrichment analysis showed that it was associated with extracellular matrix， viral infection， immune regulation， angiogenesis， and other functions and pathways， and was highly correlated with immunomodulatory molecules（ FDR＜0.05）. PVRL2 expression was associated with multiple immune cell infiltrates and most immunomodulatory genes with a statistical difference（ P＜0.05）. Conclusions High PVRL2 expression correlates with clinical grade and poor prognosis of gliomas and is strongly associated with immune regulation.