Thus, we report a case of a 56-year-old HIV-negative Chinese man, with a high levels of anti-IFN-γ autoantibodies, simultaneously diagnosed disseminated Mycobacterium tuberculosis and Talaromyces marneffei co-infection by using metagenomics next-generation sequencing (mNGS), aims to attract clinical attention and attempts to study the possible immune deficiency mechanism of anti-IFN-γ autoantibodies. This evidence concerns the gene IFNG and Immunodeficiency.