[Objective] To understand the basic characteristics of the genome sequence of the representative strain of Staphylococcus aureus from dairy cows with mastitis in Ningxia, and to further explore its drug-resistant genotype, virulence and evolutionary relationship, to serve as a theoretical basis for veterinary clinical prevention and treatment. [Methods] In total 97 clinical isolates of S. aureus were tested for antimicrobial susceptibility by the paper disk method. Staphylococcal protein A typing and multi-site sequence typing were done at the same time. According to the typing results, 16 representative strains were sequenced and the obtained sequences were analyzed by network database. [Results] Drug susceptibility test shows that 97 strains were resistant to 18 antibacterial drugs, of which 9 strains of methicillin-resistant Staphylococcus aureus (MRSA) were completely resistant to 8 antibacterial drugs, such as penicillin, ampicillin, oxacillin, ceftiofur, sulfisoxazole, erythromycin, gentamicin, and clindamycin. Methicillin-sensitive Staphylococcus aureus (MSSA) strains were highly resistant to penicillin, ampicillin, and sulfisoxazole. Antibiotic resistance genes database (ARDB) annotation analysis shows that 16 representative strains carried 21 drug resistance genes, among which the carrying rates of norA, tet38, bacA, and mepA were higher, correlating with to the results of drug sensitivity test. Virulence Factors Database (VFDB) annotation analysis shows that all strains carried a variety of virulence genes related to diseases such as adhesion, host immune escape, secretion, extracellular enzyme encoding, and iron uptake. MRSA strains all carried more virulence factors, MSSA strains carried different number of virulence factors. The results of gene island prediction show that 16 representative strains had different number of gene islands, and MRSA strains carried more gene islands and virulence gene islands, but the number of drug resistance gene islands was not significantly different from that of MSSA. The results of SNP analysis show that some isolates had higher homology, and the two MRSA with higher homology had little differences in the basic sequence characteristics of the whole genome, both carried similar resistance and virulence genes. [Conclusion] The drug resistance of S. aureus isolates from cattle in Ningxia is serious and highly virulent. Our findings provide a reference for the comparative analysis of genome sequence information of livestock-associated MRSA (LA-MRSA) and MSSA, and the clinical prevention and control of S. aureus infection in Ningxia.