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Enterovirus A71 (EV-A71) inactivated vaccines have been widely inoculated among children in Kunming City after it was approved. However, there was a large-scale outbreak of Enteroviruses (EVs) infection in Kunming, 2018.The epidemiological characteristics of HFMD and EVs were analyzed during 2008 to 2018, which are before and three years after EV-A71 vaccine starting to use. The changes of infection spectrum were also investigated, especially for severe HFMD in 2018.The incidence of EV-A71 decreased dramatically after EV-A71 vaccine starting use. The proportion of non CV-A16/EV-A71 EVs positive patients raised up to 77.17% to 85.82%, while, EV-A71 and CV-A16 only accounted for 3.41% to 7.24% and 6.94% to 19.42% in 2017 and 2018. CV-A6 was the most important causative agent in all clinical symptoms (Severe HFMD, HFMD, Herpangina and fever), accounting from 42.13% to 62.33%. EV-A71 only account for 0.36% to 2.05%. In sever HFMD, CV-A6 (62.33%), CV-A10 (11.64%), CV-A16 (10.96%) were the major causative agent in 2018. EV-A71 inactivated vaccine has a good protective effect against EV-A71 and induced EVs infection spectrum changefully. EV-A71 vaccine has no or insignificant cross-protection effect on CV-A6, CV-A10 and CV-A16. Herein, developing 4-valent combined vaccines is urgently needed.