The B6-hBAFF (TNFSF13B) mouse is a humanized model generated using gene editing technology, in which the protein-coding sequence (CDS) encoding the extracellular domain of the human TNFSF13B protein is integrated into a specific site within the mouse Tnfsf13b gene, while retaining the endogenous gene sequence encoding the mouse cytoplasmic and transmembrane domains (aa.1-68). Homozygous B6-hBAFF (TNFSF13B) mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of autoimmune diseases and specific B cell malignancies and for the development of BAFF-targeted drugs.