DNA-PKcs is a nuclear protein serine/threonine kinase which plays a pivotal role in the non-homologous end-joining (NHEJ) pathway for DNA double-strand break (DSBs) repair . Recently, series of studies have characterized that DNA-PKcs can also act as molecular promoter to control a wide array of cellular functions, such as cell cycle, metabolism, hypoxia, inflammatory response [16–19]. Activation of DNA-PKcs regulates various tumor-promoting molecules, such as maintaining the stability of Snail1, Chk1–Claspin complex, or enhancing the transcriptional activity of p53 and androgen receptor (AR), and resultantly mediates the progression of colon cancer, prostate adenocarcinoma, hepatocellular carcinomas (HCC) and other human cancers [20–23]. However, the role of DNA-PKcs in glioma progression remains to be elucidated.