Abstract: Objective To analyze the genotype distribution and genetic evolution of coxsackievirus A10 (CA10) isolated in mainland China, 2004-2016, and to provide a scientific basis supporting for prevention and control of hand-foot-and -mouth disease. Method MEGA 6.0 software was used to analyze the VP1 gene sequence of CA10 isolates from mainland China through retrieving the GenBank nucleotide database. Besides, the phylogenetic tree was constructed and the homology of nucleotide and amino acids were calculated. Results A total of 218 Chinese CA10 isolates were included in this study. Most of Chinese CA10 isolates emerged from 2004 to 2016 belonged to genotype C. Comparing with the ptototype strain CA10-Kowalik, the homology of nucleotide sequences and amino acid sequences of VP1 gene of 218 Chinese isolates were 69.4%-73.9% and 90.6%-93.6%, respectively; Moreover, the nucleotide and the amino acid homology of VP1 gene of 218 Chinese CA10 isolates among themselves ranged from 76.4% to 100.0% and ranged from 92.9% to 100.0%, respectively. Conclusions This study suggests that effective measures should be taken to prevent hand-foot-and-mouth disease according to the tendency of molecular epidemiology and genotype distribution of CA10 strains isolated in China.