Objective Cyclin-dependent kinase inhibitor 2A/B （CDKN2A/B） homozygous deletion is rare in histopathological grade 2 or 3 lower-grade gliomas， and it is a grade IV malignancy based on the new WHO classification of tumors. This study aims to investigate the clinical features， prognosis， and related functional pathways in lower-grade gliomas with CDKN2A/B homozygous deletion.Methods Clinical data were collected from 473 patients with lower-grade gliomas with CDKN2A/B homozygous deletion information who had complete clinical and prognostic data， and a statistical analysis was performed for incidence rate， clinical features， and prognosis. A total of 27 fresh tumor specimens were collected， among which there were 13 specimens with CDKN2A/B homozygous deletion， and immunohistochemistry for Ki-67 and CD31 was used to analyze cell proliferation and angiogenesis. Functions and pathways associated with CDKN2A/B homozygous deletion were analyzed based on the RNA sequencing data of 1 116 glioma cases.Results The incidence rate of CDKN2A/B homozygous deletion was 7.2% （34/473） in lower-grade gliomas， with a higher incidence rate in patients with older age， astrocytoma， grade 3 gliomas， near-total resection， or wild-type IDH （all P <0.05）. CDKN2A/B homozygous deletion was associated with shorter overall survival and progression-free survival in IDH mutant patients or IDH wild-type patients. The protein expression levels of Ki-67 and CD31 in patients with CDKN2A/B homozygous deletion were significantly higher than those in wild-type patients （P = 0.045 and 0.058）. The bioinformatics analysis showed that CDKN2A/B homozygous deletion was associated with the functions and pathways such as activated DNA replication， repair， and cell cycle.Conclusions CDKN2A/B homozygous deletion is associated with the poor prognosis and malignant phenotype of patients with lower-grade gliomas， and these patients should receive active treatment in clinical practice.