Abstract:[Background] In June 2021, a sick piglet in Maoming, Guangdong, which had pustules, swollen joints of limbs, and pus in the joints, was detected. [Objective] To identify the pathogen for the piglet, analyze its antimicrobial susceptibility, and thus to guide the clinical medication. Moreover, to analyze the whole genome sequence of the isolated strain, explore its virulence factors and antimicrobial resistance genes, thereby revealing its molecular mechanism of pathogenicity and antimicrobial resistance. [Methods] Bacteria were isolated from the joint pus. The bacterial species was identified by Gram staining, 16S rRNA gene and whole genome sequencing. The hemolysis activity, coagulase activity, and growth characteristics of the isolated strain were determined based on hemolysis test, coagulase test, and growth curve, respectively. The pathogenicity of the strain was evaluated with a mouse model. The antimicrobial susceptibility of the strain was determined by disk diffusion test. Whole genome sequence analysis was performed to explore virulence factors and antimicrobial resistance genes of the strain. [Results] The isolated strain was identified as Staphylococcus hyicus. The strain was non-hemolytic, displayed no coagulase activity, and grew well in Tryptic Soy Broth at 37℃ under shaking conditions (120 r/min). The strain exhibited high pathogenicity, and was sensitive to seven antimicrobials including oxacillin and spectinomycin and resistant to nine antimicrobials including penicillin G and erythromycin. It carried a number of virulence factors and antimicrobial resistance genes. [Conclusion] A S. hyicus strain was isolated from the joint pus of a diseased piglet. Antimicrobials such as oxacillin and spectinomycin can be used for the prevention and control of the infection caused by this strain. Furthermore, whole genome sequencing analysis was performed for this strain, which laid a foundation for further research on its molecular mechanism of pathogenicity and antimicrobial resistance.