TM is the only dimorphic fungus known to be pathogenic in mammals (including humans). Immunocompetent populations can be infected with TM; however, infections are most common in patients with defective CD4 + T-cell activity. The lungs are the main target organ of this pathogenic fungus, which can spread to other organs via lymphatic or hematogenous dissemination and progress rapidly, with a morbidity and mortality rate of up to 20% if antifungal therapy is not administered promptly. Therefore, the respiratory system is the “window” through which TM spreads to the whole body. Currently, there are few systematic analyses of the risk factors and vulnerability of HIV-negative children to TM infection. Furthermore, the clinical features in children with TM infection are nonspecific, meaning that they are not easily identified and can lead to misdiagnosis and underdiagnosis. Currently, there are no standard treatments for TM infection. Therefore, this study reviewed and analyzed the clinical manifestations of TM infection in HIV-negative children, with the respiratory system as the first location of symptoms, and analyzed the risk factors associated with infection. The children with TM infection in this study were mainly males, with the youngest age of infection being 8 months. All the children had cough and hepatosplenomegaly, and fever was the most common symptom. Moreover, two cases had hoarseness, wheezing, and hemoptysis separately when the infection involved the pharynx and airway. These features were consistent with previous reports. Previous studies have confirmed that inhalation is the main mode of TM invasion into the body, and the lung is the most important organ for TM infection. Furthermore, TM avoids phagocytosis by macrophages by adhering to bronchial epithelial cells via adhesion to the extracellular matrix while producing superoxide dismutase and peroxidase to prevent digestion by lysosomes. However, engulfed TM proliferates within macrophages and activates the pro-inflammatory cytokine IL-16, which propagates through the reticuloendothelial system, causing lymphadenectasis and multi-organ damage. In this study, P6 developed phagocytic syndrome due to the strong inflammatory response experienced after infection, which was considered to be related to the inflammatory “waterfall effect” produced by TM-mediated activation of inflammatory cytokines.