Ubiquitination is one of the pervasively studied ways of post-transcriptional modifications (PTMs)， which orchestras a plethora of physiological events，including cell mitosis，cell differentiation，cell growth， transcriptional controls，DNA damage repair and immune responses. Recently，a constitutive member of "The Ubiquitin Kingdom" called DUB (deubiquitylating enzymes) has come into the center of the stage. As an iso-peptidase，DUBs govern distinct structures and various functions. Meanwhile，the topic of gene expression control has always been the cutting edge of life sciences. It is of great importance to summarize the relationships between DUBs and gene expression regulations. In this review，we summarize the roles that DUBs play in three fields: First，chromatin regulation. Second，cell cycle control. Third，DNA damage response. Finally，we discussed and predicted the potential perspectives.