Enterovirus 71 (EV-A71) is one of the most pathogens to hand, foot, and mouth disease (HFMD) as well as neurological complications in young children. Molecular characteristic of EV-A71 is important to prevent the virus outbreak. Here, the complete genomes of EV-A71 from China between 1998 and 2019 were downloaded from GenBank. The phylogenetic trees were developed by MEGA7.0 software, and the complete genetic epidemiological characteristics and amino acid mutations of EV-A71 from China were also analysed. The results showed that major epidemic EV-A71 subtype was C4b before 2004, while it turned to C4a after 2004 in mainland China, and C4 and B5 were major subtypes in Taiwan. VP1, VP4, 2C, 3C, 3D, and complete genome sequence can be used for virus genotyping, and VP1, VP4, and complete genomes have obvious advantages over other segments. There were many significant mutations in the viral complete genome sequence. This study indicated that the major C4 and B5 subtypes will contribute to the development of vaccines and drugs of EV-A71 for prevention and monitoring of EV-A71-associated HFMD in China.