To give a new perspective on the evolutionary characteristics shaping the genetic diversity of enterovirus 71 (EV71) and the effects of natural selection from its host on the codon usage pattern of the virus, the relative synonymous codon usage (RSCU) values, codon usage bias (CUB) values, effective number of codons (ENCs) values and nucleotide contents were calculated to implement a comparative analysis to evaluate the dynamics of the virus evolution. The characteristics of the synonymous codon usage patterns and nucleotide contents of EV71 and the comparison between ENC values for the whole coding sequence of EV71 and that of coding sequences for viral proteins of EV71 all indicate that the interaction between mutation pressure from virus and natural selection from host exists in the processes of evolution of EV71. The synonymous codon usage pattern of EV71 is a mixture of coincidence and antagonism to that of host cell. In addition, the genetic diversity of EV71 strains and the preferential selection of some synonymous codons in EV71 strains based on the different epidemic areas were observed, suggesting that geographic and social factors may play roles in influencing the evolution of this virus.