Objective To understand the changes in occurrence and etiology of hand-foot-and-mouth disease (HFMD) before and after enterovirus 71 (EV-71) vaccination in Jining City from 2012 to 2021. Methods Occurrence and etiology of HFMD in Jining City were analyzed by descriptive epidemiological methods. Changes in incidence and pathogens of HFMD before and after EV-71 vaccination were compared. Results From 2012 to 2021, incidence of HFMD among children aged 6 months-5 years in Jining City was 658.93/100 000, the highest incidence was 1 094.63/100 000 in 2018, and the lowest incidence was 247.23/100 000 in 2021. In laboratory diagnosis cases, EV-71, coxsackievirus A16 (CV-A16), and non-EV-71 non-CV-A16 accounted for 27.89%, 34.59%, and 37.52% respectively. Among children aged 6 months to 5 years, the estimated incidence of EV-71 was 131.04/100 000, the highest estimated incidence was in 2017 (322.13/100 000), and the lowest estimated incidence was in 2021 (7.71/100 000). EV-71 was the main type of severe cases, accounting for 76.25%. The estimated vaccination rate of EV-71 vaccine in Jining City from 2016 to 2021 was 7.98% on average. After EV-71 vaccination, the proportion of EV-71 HFMD was lower than that before vaccination, with a decrease of 4.80%. The dominant strain in 2013 and 2017 was EV-71, the proportion of EV-71 began to decrease in 2018, and the lowest was 5.16% in 2021. Conclusion Vaccination rate of EV-71 vaccine in Jining City is relatively low. After inoculation of EV-71 vaccine, the estimated incidence of EV-71 reached the peak in 2017, but then showed a downward trend. The majority of virus strains were CV-A16 and non-EV-71 non-CV-A16, it is necessary to further carry out typing of non-EV-71 non-CV-A16, and develop multivalent HFMD vaccine.