Background:  Staphylococcus aureus (S. aureus) represents a substantial public health concern due to its progressive development of antimicrobial resistance. Its virulence is significantly contributed to the released toxins. This study aimed to assess toxin encoding genes (sea, hla and pvl) and the prevalence of Methicillin-resistant S. aureus (MRSA) among S. aureus isolates gathered from Ain Shams University (ASU) Hospital and determine possible correlation of these genes with antibiotic resistance. Methods: A total of 94 isolates were obtained from various clinical departments and samples. The process of identifying the isolates was carried out utilizing standard procedures. Disc diffusion method was utilized for testing antimicrobial susceptibility. Conventional PCR was utilized for detection of sea, hla and pvl genes. Results: MRSA prevalence among collected isolates was 78.7%, ICU was significantly more frequent in MRSA. Vancomycin, linezolid and doxycycline were the most effective tested antibiotics. Isolates showed high prevalence of three genes: sea, hla genes 93.6%, pvl gene 86.2%. The three genes collectively detected in 79.8% of isolates. Both hla and pvl genes were significantly more frequent in MRSA. Positive hla and pvl genes isolates had significant more frequent resistance to beta lactams, erythromycin, ciprofloxacin and levofloxacin. In addition, positive pvl gene isolates had significant more frequent resistance to trimethoprim-sulfamethoxazole and gentamycin. Conclusion: This research reports high prevalence of MRSA isolates in ASU hospitals. A high resistance rate to antibiotics was observed in positive pvl, then in hla positive isolates. Presence of either gene may indicate increased rate of resistance to antimicrobials.