EV71 vaccine immunization mainly protects the human population against severe and fatal HFMD and has a positive effect on reducing the overall incidence rates of HFMD and of hospitalized cases. In the analysis of data collected over 4 years, we compared HFMD’s incidence rate, severity, and etiological changes in a target population before and after vaccine intervention. The incidence rate of HFMD decreased from 39.02‰ in 2014 to 11.02‰ in 2021, with a decrease rate of 71.7%, and the decrease was statistically significant (p< 0.001). The number of hospitalized cases decreased by 68.88%, the number of severe cases dropped by 95.60% and the number of deaths dropped to 0. The proportion of cases caused by the EV71 virus in different populations decreased significantly after the intervention, specifically, by 68.41% among individuals 0–4 years of age, by 74.32% among kindergarten children, by 86.07% in severe cases and by 100% with respect to the number of deaths.