Immunodeficiency animal models play an important role in preclinical research and are important experimental tools in modern biomedical research, widely used in immunology, genetics, oncology and microbiology, and other research fields. Gene editing is a technology of targeted modification of biological genomes, from emergence to application, it has greatly promoted the development of biomedical research. Gene editing technology mainly includes homing endonucleases (HEs), zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9 systems. At present, researchers has used these technology to establish a variety type of immune deficiency animal models, each with its own advantages and limitation. In recent years, a large number of studies have confirmed that the human immunodeficiency animal model can accurately simulate the function of cancer cells, drugs and immune system in human body, and can better simulate human diseases, and is widely used in the study of human immunobiology and the potential mechanism of human complex diseases. In this paper, we reviewed the progress in the research and application of gene editing technology in the construction of immune deficiency animal models, discussed the problems and optimization strategies of gene editing technology in the preparation of immune deficiency animal models in depth, and prospected its future development prospects, in order to provide references for researchers to select and build immune deficiency animal models.