The interaction between co-stimulatory ligands and their receptors of T cells and antigen presenting cells is crucial for the activation or resting of the immune cells. The tumor necrosis factor receptor superfamily and CD28-B7 family contain many such regulatory molecules. Herpesvirus entry mediator (HVEM), also named as tumor necrosis factor superfamily member 14, is noted for its pivotal role in regulating immune responses through binding LIGHT as a ligand to develop T-cell immunity, and in interacting with B and T lymphocyte attenuator(BTLA) as a receptor to negatively regulate T-cell responses. In antitumor immunity, increasing amount of evidence demonstrates that HVEM is an indispensable receptor on lymphocyte for LIGHT to co-stimulate tumor antigen-specific CTL. This article discusses the role of HVEM in regulating immune response and antitumor-immunity.