Staphylococcus aureus is a common etiological factor in infections of burns and other chronic wounds. The development of an effective and fast-acting treatment would be enormously beneficial and is highly desired. We focused on testing the bactericidal efficacy of photoinactivation using a known photosensitizer (protoporphyrin IX, PPIX) in sequential combination with silver nanoparticles against S. aureus. Using PPIX-based photoinactivation followed by silver nanoparticles we obtained a high bactericidal effect (7 log10 units reduction) with limited harmful effects on human epidermal keratinocytes. Moreover, we observed that the use of silver nanoparticles prevents bacterial re-growth 24 h post-PDI treatment. A sequential combination of photoinactivation and silver nanoparticles represents a potentially effective antibacterial approach.