Aim:Glioma is the most common primary tumor of the brain and spinal cord. Postoperative adjuvant radiotherapy and chemotherapy are conventional treatment methods. Resistance to these methods drives poor prognosis. CBX8, an important part of the polycomb inhibition complex, plays a significant role in various malignant tumors. However, its role has not been clearly reported, especially within DNA damage repair pathways.Material and Methods:Detect CBX8 expression in glioma cells and clinical samples by qPCR and Western blot. Overexpression and knockdown CBX8 cell lines were constructed by lentivirus infection. CCK8, wound healing, and transwell assays were used to verify the effects of CBX8 on proliferation, migration, and invasion of glioma cells. After radiation treatment, CCK8 and colony formation assays were used to detect cell sensitivity of CBX8 expression levels to radiotherapy. Western blot detected expression levels of p-ATM, p-ATR, BRCA-1, RAD51, and P53 in various cells after radiation treatment, demonstrating CBX8’s effect on DNA damage and repair proteins. Finally, the sensitivity of tumors with different CBX8 expression levels to radiotherapy was verified in vivo.Results:CBX8 expression is significantly increased in glioma. High CBX8 expression promotes proliferation, invasion, and migration of glioma cells. It also causes glioma cells to resist radiotherapy. CBX8 affects protein expression related to DNA damage repair. In vivo, tumors with low CBX8 expression are more sensitive to radiotherapy.Conclusion:CBX8 promotes proliferation and metastasis of glioma cells and reduces cell sensitivity to radiotherapy by affecting DNA damage repair pathways.