Enhancers constitute a vital category of cis-regulatory elements with a Mediator complex within DNA sequences, orchestrating gene expression by activating promoters. In the development of T cells, some enhancers regulate the critical genes, which might also regulate T cell malignant lesions. This review is to comprehensively elucidate the contributions of enhancers in both normal T cell development and its malignant pathogenesis, proposing the idea that the precise subunits of the Mediator complex are the potential drug target for disrupting the specific gene enhancer for T cell malignant diseases.