Objective The aim of this study was to screen enterovirus 71(EV71) pathogenicity-related genesusing genetic diversity mice to further understand the pathogenesis of the EV71, and lay the foundation for clinicaldiagnosis, treatment and prognosis. Methods Four-to-six week old genetic diversity mice were challenged with 10⁷copiesof enterovirus 71 by intraperitoneal injection. The blood and hind limb skeletal muscles were collected, and the viral loadwas determined by real-time quantitative PCR. Then, the GeneMine system genetic database was used to analyze theinfection data, and EV71 pathogenicity-related genes were screened. Results Fifty-three genes related to EV71 infectionwere screened using genetic diversity mouse infection data. Conclusions Genetic diversity mice have significantadvantages for simulating population genetic diversity and are a new resource to study complex trait diseases. Mostimportantly, they are an ideal and efficient resource for the screening of pathogenicity-related genes.