Carotid stenosis is a narrowing or constriction of the inner surface of the carotid artery, usually caused by atherosclerosis. In the past decades, carotid angioplasty and stenting (CAS) has been developed into a credible option for the patients with carotid stenosis. However, restenosis remains a severe and unsolved issue after CAS treatment. Currently, the molecular mechanisms involved in the restenosis are still largely unclear. In this study, we found that the double-strand DNA breaks (DSBs) were induced by oxidative stress in the human carotid artery with restenosis by examining the level of γH2AX in the artery tissues. We further analyzed the activation of DNA damage repair pathways in the carotid restenosis. Our results suggest that non-homologues end joining (NHEJ), but not homologous recombination (HR), is mainly activated in the artery tissues with restenosis. Our results may provide clues to develop a new therapeutic strategy for carotid artery restenosis following CAS treatment.