The B6-hCD20 mouse is a humanized model generated using gene editing technology to replace the entire base sequence of the mouse Ms4a1 gene in situ with the corresponding sequence from the human MS4A1 gene. Homozygous B6-hCD20 mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of autoimmune diseases and cancers, and for the screening, development and preclinical efficacy and safety evaluation of CD20-targeted drugs.