The pathophysiology of HLH involves excessive immune activation and cytokine storm, but the underlying mechanism of TB-HLH remains unclear, although TB infection disrupts immune homeostasis leading to secondary HLH. In patients with TB, the levels of interferon-γ, tumor necrosis factor-α, and granulocyte/monocyte colony-stimulating factor are higher than those in a healthy population. Moreover, in HLH patients with cytokine storm, the increased levels of cytokines mentioned above along with macrophage colony-stimulating factor and interleukin (IL) family cytokines, including IL-1, IL-6, and IL-18 among others, are important markers. Specifically, Mycobacterium tuberculosis could act as an obligate intracellular pathogen after phagocytosis by phagocytic cells to induce TH1-mediated cytotoxicity, activating macrophages and NK cells, further releasing a large quantity of cytokines and chemokines, leading to TB and HLH-related symptoms. Meanwhile, M tuberculosis can induce migration of monocytes and macrophages to regional lymph nodes through a mechanism mediated by IL-12 and IL-15, leading to antigen-specific T-cell expansion, stimulation of persistent cytokine release, followed by subsequent activation and proliferation of macrophages.[10–13]