Abstract: Ubiquitination is a crucial post-translational modification process that can degrade proteins within cells and plays a vital role in maintaining protein homeostasis and abundance. Deubiquitinating enzymes (DUBs) are important proteases in the ubiquitin system. They reverse the ubiquitination process by cleaving protein chains and recycling ubiquitin molecules to regulate protein stability. Abnormal deubiquitinating enzyme activity is related to the occurrence and development of many malignant tumors. JOSD2, a DUB, is a member of the Machado-Joseph disease protein domain protease (MJD) family and characterized by a single highly conserved catalytic Josephin domain. Increasing studies have revealed a connection between JOSD2 and malignant tumors. This article elaborates on the current research status of DUBs, particularly JOSD2, in malignant tumors. Results suggest that JOSD2 is a potential target for the treatment of malignant tumors.