Therefore, in this study, we collected human GBM transcriptome data from The Cancer Genome Atlas (TCGA-GBM dataset) and performed a systemic analysis for characterizing the functional role of HDAC6 in DDR pathways, including not only HR, BER, MMR, but also nucleotide excision repair (NER), nonhomologous end joining (NHEJ), etc. Also, we used in vitro experiments and intracranial mouse models for targeting HDAC6 via pharmacological approaches and genetic knockdown to further examine the role of HDAC6 on the DDR regulation in both TMZ-sensitive and TMZ-resistant GBM. This evidence concerns the gene HDAC6 and glioblastoma.