Staphylococcus aureus causes diseases ranging from fairly minor skin and soft-tissue infections to dangerous sepsis [1,2]. All penicillins are ineffective against MRSA, including cephalosporins, carbapenems, semi-synthetic penicillinase-resistant congeners, and penems. Once methicillin was discovered in 1960, resistant strains were named after the showing of clinical isolates in England by 1967. MRSA was described in several countries primarily in the early 1980s. MDR-MRSA has been reported in numerous countries and is presently endemic in many hospitals worldwide, and commonly in developing countries such as Brazil [3].Because of the increased mortality related to MRSA infections, the emergence of strains resistant to methicillin and other antimicrobials has become a major concern, particularly in the hospital context [2]. Between 1999 and 2002, increases in methicillin resistance were found in S. aureus isolates in European nations, namely Belgium, Germany, Ireland, the Netherlands, and the United Kingdom. In Northern, Western, and Southern Europe, MRSA incidence ranged from 1% to 40%, respectively [4].The need to halt the spread of MRSA and decrease the incidence of MRSA infections in hospital settings now appears critical, as the multidrug-resistant organism's prevalence persists. According to a recent study, the average MRSA transporter ratio among healthcare workers is 4.6%, with 5.1% having typical MRSA infections. MRSA levels must also be controlled by healthcare staff [2].Staphylococcus aureus is a cause of high mortality in humans and therefore it is necessary to prevent its transmission and reduce infections. Our goals in this research were to investigate the frequency of methicillin-resistant S. aureus (MRSA) in Taif, Saudi Arabia, and assess the relationship between the phenotypic antimicrobial sensitivity patterns and the genes responsible for resistance. In addition, we examined the antimicrobial efficiency and application of silver nanoparticles (AgNPs) against MRSA isolates. Seventy-two nasal swabs were taken from patients; MRSA was cultivated on Mannitol Salt Agar supplemented with methicillin, and 16S rRNA sequencing was conducted in addition to morphological and biochemical identification. Specific resistance genes such as ermAC, aacA-aphD, tetKM, vatABC and mecA were PCR-amplified and resistance plasmids were also investigated. The MRSA incidence was ~49 % among the 72 S. aureus isolates and all MRSA strains were resistant to oxacillin, penicillin, and cefoxitin. However, vancomycin, linezolid, teicoplanin, mupirocin, and rifampicin were effective against 100% of MRSA strains. About 61% of MRSA strains exhibited multidrug resistance and were resistant to 3-12 antimicrobial medications (MDR). Methicillin resistance gene mecA was presented in all MDR-MRSA strains. Most MDR-MRSA contained a plasmid of > 10 kb. To overcome bacterial resistance, AgNPs were applied and displayed high antimicrobial activity and synergistic effect with penicillin. Our findings may help establish programs to control b...