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Ubiquitin specific proteases 22 (USP22) is a highly conserved ubiquitin hydrolase in mammals. It mainly prevents proteins degradation by deubiquitinating substrate proteins and regulates life processes such as genetic transcription, DNA damage repair and embryonic development. USP22 has been proved to promote cancer development by regulating multiple signal pathways. This article focuses on the relevant mechanisms of USP22 regulating tumorigenesis and development through deubiquitinating modification.