Lymphotoxin α, β and its receptor (LTAR,LTBR) belong to the tumor necrosis factor superfamily. LTBR signaling has a variety of physiological functions. It includes controlling the development of lymphoid organs, maintaining intact lymphoid structure, inducing immune response against pathogens, mediating the regeneration of organs and tissues, and participating in the evolution and development of tumors. The non-classical/classical nuclear transcription factor -kappaB (NF-κB) pathway through LTBR signaling induces the secretion of chemokines and adhesion molecules to promote cell proliferation and differentiation. LTBR signaling not only plays a role in autoimmune diseases, but also has different anti-cancer and pro-cancer functions through different models. In this paper, we will also focus on the regeneration mechanism of LTBR signal after organ development and related tissue damage, so as to open up a new perspective for regenerative medicine.