Objective To explore clinical characteristics of primary Cryptococcus neoformans infection in spleen. Methods The clinical data of a child with primary Cryptococcus splenococcus infection was retrospectively analyzed and the related literature was reviewed. Results　A female, 2 years and 3 months old, was admitted to hospital with persistent fever, anemia and increased eosinophils. Imaging findings revealed splenomegaly, and no history of recurrent infection was found. Physical examination showed no abnormalities in the heart, abdomen and nervous system. Abdominal CT revealed splenomegaly and multiple abdominal masses. Histopathology of spleen biopsy confirmed Cryptococcus neoformans infection in the spleen. Conclusions　Cryptococcus neoformans infection in spleen could lead to persistent fever, anemia, increased eosinophils, multiple abdominal mass and splenomegaly.