B6-hIL12B mice are humanized models generated by gene editing technology, in which the entire base sequence of the mouse Il12b gene was replaced in situ with the corresponding sequence from the human IL12B gene. Homozygous B6-hIL12B mice are viable and fertile. This model can be used to study the pathological mechanisms and therapeutic methods of immune-related diseases and cancer, as well as the screening and development of IL12B-targeted drugs, and preclinical efficacy and safety evaluations.