Staphylococcus aureus (S. aureus) as a major pathogen is implicated in a wide range of foodborne and hospital-acquired infections, its methicillin resistant variants contribute to the spread of β-lactam antibiotic resistance. It is essentially important to destroy these pathogens, their resistance genes and the antibiotics in wastewaters. For this purpose reactions of reactive radicals (advanced oxidation processes), first of all hydroxyl radicals (•OH), are suggested. Here the radiolysis of water supplied these radicals. In the experiments B.01755 oxacillin sensitive and B.02174 resistant S. aureus strains were used to study their behaviorr in suspensions under the effect of irradiation in presence and absence of oxacillin. Oxacillin inactivation depended on concentration of the antibiotic used (0.042 and 1 g dm−3), higher concentration required a higher dose. When 106–109 CFU cm−3 S. aureus suspensions were irradiated with γ-radiation the bacteria were inactivated at low absorbed doses: 4 orders of magnitude decrease ocurred in the number of culturable cells at ∼0.6 kGy dose. Both cell membrane and DNA suffered considerable damages during irradiation. Due to the membrane damage the cells could not be stained, and the DNA content of cells in several days period was released into the solution. In DNA damage the oxacillin resistance mecA gene was also modified, it did not multiply in PCR test. These findings are important from the point of view of applying irradiation technology to stop the spread of antibiotic resistance.