Objective To summarize the clinical characteristics of 2 cases of human immunodeficiency virus (HIV)-negative children suffered from Talaromycesis marneffei (TSM). Methods Clinical characteristics, laboratory data and underlying diseases of 2 HIV-negative children with TSM and treated in a children's hospital were analyzed, relevant literatures were reviewed to summarize the clinical characteristics as well as diagnosis and treatment experience of children with TSM. Results Among 2 HIV-negative children with TSM, case 1 presented the initial symptom of mass in the right lower limb, developed fever and cough more than 1 month later, and was misdiagnosed as tuberculosis infection; case 2 began with fever, with pancytopenia, hepatosplenomegaly and lymph node enlargement. Gene test of case 1 presented STAT1 gene mutation, case 2 had a history of recurrent onychomycosis and oral ulcer, which were confirmed by blood, bone marrow culture and lymph node biopsy. Case 1 was treated with intravenous drip of voriconazole and amphotericin B liposome as well as oral medications of itraconazole for maintenance therapy, medication was stopped after 1 year of treatment; case 2 had been treated with voriconazole (intravenous drip first, then oral medication) for 7 months, and there was no recurrence. Conclusion TSM can occur in HIV-negative children, and there may be STAT1 gene mutation. For children with poor treatment effect, culture or tissue biopsy should be performed as early as possible to make a confirmed diagnosis, and actively find the possible underlying diseases of TSM, so as to achieve early diagnosis, early treatment and prognosis improvement.