Ubiquitination plays an important role in many biological processes, including viral infections, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies have found that DUBs can either inhibit or enhance viral infection through various mechanisms, the role of DUBs in viral regulation is still unknown and needs to be further explored. Ubiquitin specific protease (USP) belongs to cysteine protease and is one of the important members of deubiquitination enzyme family. USP family members affect viral replication through positive or negative regulatory mechanisms in a variety of ways. For example, USP4, USP8, USP13, USP15 and USP49 have antiviral effects, while USP1, USP7, USP33 and UL36USP negatively regulate the antiviral immune response of the body. This review aims to comprehensively summarize the regulatory mechanisms and research progress of USP family members in antiviral immune response, which not only reveals the complex role of these proteases in virus-host interactions, but also provides valuable molecular targets and theoretical basis for the development of novel antiviral strategies. With the deepening of research, the multifaceted nature of USPs in virus infection and prevention and control will gradually become clear, offering new solutions to global public health challenges.