Objective To understand the effect of EV71 vaccination on the epidemiology and pathogen of hand-foot-and-mouth disease (HFMD), and provide scientific basis for the prevention and treatment of HFMD. Methods Data of children with HFMD in a hospital from 2014 to 2018 were collected, SPSS 18.0 software was used to analyze the data, epidemiological characteristics and change in pathogens of HFMD in hospitalized children before and after EV71 vaccination were compared. Results A total of 7 099 children with HFMD were admitted in the hospital, including 6 339 cases of common type and 1 570 cases of severe type, compared with children before EV71 vaccination, the number of hospitalized children with HFMD after vaccination decreased, proportion of severe cases decreased (χ²=56.27, P<0.001). Incidence of HFMD in boys was higher than girls, onset age was still dominated by infants under 5 years old, but the number of severe cases in each age group all decreased; there were two onset peaks in the whole year, which was May-July and September-November respectively; common cases were mainly EV71/CoxA16 infection, while severe cases were mainly EV71 infection. Conclusion The dominant pathogen of HFMD changes significantly after EV71 vaccination, and proportion of severe cases decrease significantly, EV71 vaccine is worth to be popularized and applied. In order to provide a more powerful basis for the prevention and treatment of HFMD, it is necessary to further develop the typing detection of non-EV71/CoxA16 enteroviruse.