Abstract: Non-tuberculous mycobacteria （NTM） are opportunistic pathogens that often infect the immunosuppressed individuals. NTM osteomyelitis is a rare disease, mostly as part of disseminated infection. In this article, the diagnosis and treatment of an AIDS patient complicated with NTM osteomyelitis of the lower tibia were reported. The 40-year-old female patient was admitted due to the left ankle pain during antiretroviral therapy. According to blood culture test and imaging examination, the patient was diagnosed with Talaromyces marneffei osteomyelitis before surgery. Postoperative pus culture was positive for NTM. She was pathologically diagnosed with NTM osteomyelitis. After multiple cycles of surgical treatments and more than 1 year of postoperative follow-up, the patient was physically stable. The diagnosis and treatment of this case prompt that the diagnosis of NTM osteomyelitis should be considered for AIDS patients presenting with rapidly-progressive osteomyelitis. The diagnosis depends on the culture of pathogens. Prompt surgical debridement and anti-NTM treatment based on drug sensitivity test are of significance for clinical prognosis.