Objective The prognostic significance of chondroitin polymerization factor 2 (CHPF2) in glioma was analyzed by bioinformatics technology, and its expression in normal and glioma cells was further verified by experiments. Methods The expression levels of CHPF2 in glioma and normal cells were first analyzed in the GEPIA and HPA databases, followed by downloading gene expression and clinical information files from The Cancer Genome Atlas (TCGA) and The Chinese Glioma Genome Atlas (CGGA) to further elucidate the expression, prognosis, functional annotation, immune infiltration, and immune checkpoints of CHPF2 in glioma. Finally, the expression levels of CHPF2 in normal and glioma tissues were determined using the Western blotting approach. Results CHPF2 expression in gliomas was greater than in normal tissues, and it increased with tumor grade. Except for gender, radiation, and tumor recurrence, the high and low CHPF2 expression groups differed statistically in age, chemotherapy, tumor recurrence, IDH, 1p/19q, and MGMT. CHPF2 outperforms certain popular prognostic markers (e.g. TP53, MKI67, and EGFR) in predicting glioma patient survival and may be utilized as an independent prognostic factor. A complete meta-analysis of the outcomes of separate prognostic analysis of the TCGA and CGGA databases corroborated this further. GO, KEGG, and GSEA techniques were used to examine the pathways for which CHPF2 may be enriched. Initially, three approaches (TIMER, CIBERSORT, and ssGSEA) were utilized to investigate immune infiltration in the high and low-risk groups of CHPF2, and finally, the immunological checkpoints of CHPF2 were examined. To further corroborate the dependability, Western blotting was used to demonstrate the elevated expression of CHPF2 in gliomas relative to normal tissues. Conclusion CHPF2 may be able to influence the occurrence, progression and prognosis of glioma and may serve as a biomarker for the prognosis of glioma patients. [ABSTRACT FROM AUTHOR]