Staphylococcus aureus is a common human pathogen with a variety of virulence factors, which can cause multiple infectious diseases. In recent decades, due to the constant evolution and the abuse of antibiotics, Staphylococcus aureus was becoming more resistant, the infection rate of MRSA remained high, and clinical treatment of MRSA became more difficult. The genetic diversity of MRSA was mainly represented by the continuous emergence of epidemic strains, resulting in the constant changes of epidemic clones. Different classes of MRSA resulted in different epidemics and resistance characteristics, which could affect the clinical symptoms and treatments. MRSA had also spread from traditional hospitals to community and livestock environments, and the new clones established a relationship between animals and humans, promoting further evolution of MRSA. Since the resistance mechanism of MRSA is very complex, it is important to clarify these resistance mechanisms at the molecular level for the treatment of infectious diseases. We firstly described the diversity of SCCmec elements, and discussed the types of SCCmec, its drug resistance mechanisms and expression regulations. Then, we described how the vanA operon makes Staphylococcus aureus resistant to vancomycin and its expression regulation. Finally, a brief introduction was given to the drug resistance mechanisms of biofilms and efflux pump systems. Analyzing the resistance mechanism of MRSA can help study new anti-infective drugs and alleviate the evolution of MRSA. At the end of the review, we summarized the treatment strategies for MRSA infection, including antibiotics, anti-biofilm agents and efflux pump inhibitors. To sum up, here we reviewed the epidemic characteristics of Staphylococcus aureus, summarized its classifications, drug resistance mechanisms of MRSA (SCCmec element, vanA operon, biofilm and active efflux pump system) and novel therapy strategies, so as to provide a theoretical basis for the treatment of MRSA infection.