Objective To understand the genetic diversity and antimicrobial resistance characteristics of Salmonella enterica Serovar Enteritidis (SE) isolated from foodborne disease surveillance in Sichuan Province from 2020 to 2021, and to compare the consistency between the predicted phenotype of antimicrobial resistance and the results of antimicrobial susceptibility test, so as to provide reference for outbreak warning and antimicrobial resistance prediction based on WGS. Method A total of 222 strains of SE isolated from foodborne disease surveillance from 2020 to 2021 were analyzed by WGS, the single nucleotide polymorphism (SNP) of the strains were analyzed by snippy, and a phylogenetic tree was constructed. Using ResFinder to annotate determinants and predict antimicrobial resistance. The minimum inhibitory concentration (MIC) of the strains against 15 antibiotics was determined with a micro broth dilution method. Rerults 214 of 222 strains of SE were Group II, 4 strains each in Group I and Group III. A total of 26 suspected aggregation events were identified, mainly small point source aggregation events. Antimicrobial susceptibility tests showed that Group Ⅰ and Ⅲ of SE were susceptible to all antimicrobials tested. The Group Ⅱ of SE had different resistance to 15 kinds of antibiotics, and about 78.5% were multi-drug resistant. The predicted results for some drugs are highly consistent with the phenotype, except polymyxin. Conclusion SE strains isolated from foodborne disease surveillance in Sichuan province were mainly belonged to serogroup Ⅱ strains, which were further divided into two dominant types, SC-A and SC-B, and four non-dominant types, with high genetic diversity. Single nucleotide polymorphism typing based on WGS can detect the association and cluster of cases from SE monitoring, and provide a basis for initiating epidemiological investigations. The resistance prediction for most ordinary drug was highly consistent with the phenotype tests, but the resistance prediction of compound drugs containing more than two antibiotics and extraordinary drugs still needs to be optimized.