Graft versus host disease (GVHD) is the major complication of allogenic hematopoietic stem cell transplantation (allo-HSCT), and is a mainly responsible result for the non-recurrence-related mortality of long-term survived patient after transplantation. Studies indicated that regulatory T (Treg) cells can inhibit early-GVHD. Since the transcriptional factor NF-κB has been implicated in the regulation of Treg cell proliferation and activation, it becomes a potential target of GVHD therapy. Thus, in this review the function and signaling pathway of NF-κB, as well as the relationship between GVHD and NF-κB, are discussed and summarized.