BACKGROUND: Biocides compounds are widely used in infection control programs, including hand washing and skin decolonization before invasive procedures. However, its overuse leads to the emergence of Staphylococcus aureus with decreased biocides susceptibility, which became a problem in hospitals in different parts of the world. AIM OF THE WORK:The present work aims to study the susceptibility of methicillin-resistant isolates of staphylococci aureus, obtained from different clinical samples to commonly used biocides, determines the prevalence of the biocide resistance genes, qacA/B, and qacC, among these isolates. METHODS:Biocide's resistance genes [qacA/B, qacC] in Both Methicillin-Resistant and Methicillin-Sensitive Strains of Staphylococcus aureus were detected by PCR method. The minimum inhibitory concentrations [MICs] of Biocide agents were determined by broth dilution method, whereas antibiotic susceptibility was analyzed by disk diffusion and MICs methods according to Clinical and Laboratory Standards Institute [CLSI] criteria. RESULTS: The frequency of Biocides resistance genes [qacA/B, qacC] was found to be high in our clinical staphylococci isolates. The qacA/B gene was detected in [63.3%] of MRSA isolates compared with only [23.3%] of MSSA isolates. Simultaneously, the qacC gene was detected in [63.3%] of MRSA isolates compared to only [13.3 %] of MSSA isolates., with the significant difference between both groups [P<0.05]. We also found an association between the presence of antiseptic resistance genes qacA/B, and increased MIC values to both savlon, hypochlorite, and Phenol [P<0.05]. We also showed that an association between the presence of antiseptic resistance genes qacC and the MICs to both savlon, hypochlorite, and Phenol [P<0.05]. CONCLUSION: Our study detects biocide resistance genes [qacA/B, qacC] in Staphylococcus aureus isolates in Egypt; more studies are needed to correct the biocide uses and to support infection control programs to avoid the development of new resistance mechanisms.