Studies have found that the ubiquitin-proteasome system plays an important role in both ubiquitination and deubiquitination, and involves in many cell biological processes. As an important part of the ubiquitin-proteasome system in eukaryotic cells, deubiquitinating enzyme can directly or indirectly affect inflammation, apoptosis,proliferation and other cellular activities,and regulate the process of atherosclerosis. In view of the importance of deubiquitinating enzyme, this article reviews the role and mechanism of deubiquitinating enzyme in atherosclerosis, providing evidence for clinical diagnosis and treatment of atherosclerosis.