Glioma is a common and malignant brain tumor, and molecular diagnostics for glioma have received increasing attention.1,2 Previous studies have suggested that the MAL2 gene may be involved in the transcytosis of various cancers.3 This study aimed to investigate the potential of MAL2 as a biomarker for glioma. The candidate MAL2 CpG sites were validated by pyrosequencing and used to construct a diagnostic model for glioma. Survival analysis was also conducted to determine the relationship between highly methylated MAL2-specific CpG sites and the prognosis of glioma. The findings also showed that MAL2 was more highly methylated in glioma than in other cancers. The constructed diagnostic model can distinguish glioma from other cancers with high sensitivity (93.3%) and specificity (86.5%). Additionally, a risk score model was built based on MAL2 methylation to assess the prognosis of glioma.