Huntington’s disease (HD) is an autosomal dominant hereditary neurodegenerative disorder, caused by mutation of Htt gene which encoding huntingtin (Htt). Expanded Htt proteins form aggregates accumulated in cells and result in progressive neuronal degeneration and dysfunction. There are many hypothesis on the pathogenesis of HD, such as oxidative stress and mitochondrial dysfunction. Report on Nature in 2017 highlights that DNA repair as a shared mechanism in neurodegenerative disorders. More and more evidences indicate that DNA repair mechanisms have been implicated in Huntington’s Disease, mutant Htt triggers different types of DNA lesions and excessive activation of DNA damage response. HD is associated with cellular radiosensitivity and double strand break repair defect, and mutant Htt impact the normal function of ATM(ataxia tetangtectasia mutated) in DNA repair. Moreover, DNA repair proteins also impact the onset age of HD. Targeting ATM can ameliorates mutant Huntingtin toxicity in cells and animal models of HD. ATM has a important role in regulating celluar homeostasis and mitochondria signaling, so the mechanism of targeting ATM is more and more clear. This review introduces recent advances in HD and DNA damage response, opens a new direction for study of pathogenic mechanism and development of therapies.