Abstract: Objective　To explore the clinical characteristics of hemophagocytic syndrome (HPS) associated with Streptococcus pneumoniae. Methods　The clinical data of one child with HPS associated with Streptococcus pneumoniae was retrospectively analyzed. The relevant literatures were reviewed. Results　A 12-months boy presented with fever, cough, shortness of breath, hepatomegaly as the main clinical manifestations, and accompanied by cytopenia, hyperferroteinemia, high level of soluble IL-2 receptor and C-reactive protein, and phagocytes were observed in bone marrow. Lung imaging examination indicated lung infection, and multidrug-resistant Streptococcus pneumoniae was detected. After the treatment of antibiotics, immunoglobulin, dexamethasone, etc, the condition was improved. Four cases with relatively complete clinical data were retrieved from literature. There were three males and one female aged 3, 8, 25 and 37 years old respectively. All of the cases were accompanied by fever, and other common features include hepatomegaly, cytopenia, abnormally elevated C-reactive protein and hemophagosis. The reported infection includes two in the lung, one in the ear and one as sepsis. Two patients with severe underlying diseases had poor prognosis and the other two had better prognosis. Conclusions　When patients diagnosed with Streptococcus pneumoniae infection should be highly suspected of HPS, particularly with multi-resistant bacteria after effective antibiotic therapy, high fever, hepatosplenomegaly, cytopenia, abnormally elevated C-reactive protein. Immediate laboratory investigation is highly recommended.