Abstract: Objective　To investigate the clinical and genetic features of three patients diagnosed with hereditary spherocytosis. Methods　Clinical data of three patients with hereditary spherocytosis were collected, and genetic changes were identified by next generation sequencing, and Sanger sequencing was used to confirm mutations identified by sequencing. Results　Three cases of patients (two boys and one girl) with anaemia and jaundice, aged from 2 year and 7 months to 4year and 10 months, were treated in the outpatient department in our hospital. The clinical manifestations included skin pallor, jaundice and hepatosplenomegaly, declined hemoglomin level, increased total bilirubin, and increased reticulocyte ratio. The percentage of spherical erythrocytes in the peripheral blood was more than 10%. Erythrocyte osmotic brittleness test was positive in three patients. Genetic analysis identified two heterogenous missense mutations c.830A>G(p.H277R) and c.955C>T (p.R319X) in the ANK1 gene in two children, and a splice mutation in another patient (IVS3+1G>T). Conclusions　patient diagnosed with hereditary spherocytosis often has anemia and jaundice. ANK1 gene mutation is a common cause of the disease. We found two novel mutations that has not been reported.