Decoy receptor 3 (DCR3), also named TR6 or M68, which is a novel member of the tumor necrosis factor receptor (TNFR) superfamily, is currently reported as a deceiver to halt immune attack. Accumulating studies demonstrate that DCR3 may not only ”passively” act as a deceiver, but also ”actively” modulate an immune response that helps tumor cells escape from immune surveillance by interacting with several molecules belonging to the tumor necrosis factor (TNF) superfamily or some unidentified ligands. In this article, we summarize recent findings that describe the therapeutic potential and possible mechanisms of DCR3-mediated immune suppression and further discuss the future prospects as well as some questions that remain unanswered in the therapeutic application of DCR3. Through the understanding of DCR3 and its mechanisms, we may provide a new perspective on the regulation and/or manipulation of the immune response.