Staphyloxanthin　(STX)　is　a　virulence　factor　produced　by　Staphylococcus　aureus　(S.　aureus)　including　methicillin-resistant　S.　aureus　(MRSA),　a　widely　distributed　Gram-positive　bacterium　related　to　several　clinical　human　infections.　We　herein　reported　that　Naftifine,　a　broad-spectrum　antifungal　agent,　plays　an　important　role　on　photodynamic　antimicrobial　therapy　(PACT)　for　S.　aureus.　STX　attenuated　the　PACT　effect　on　S.　aureus　in　a　dose-dependent　manner,　which　probably　due　to　its　biological　function　of　scavenging　reactive　oxygen　species　(ROS).　On　the　contrary,　the　sensitivity　of　S.　aureus　to　PACT　was　significantly　improved　after　an　incubation　with　Naftifine　(10　mu　M)　compared　with　that　of　S.　aureus　untreated　with　Naftifine.　The　reason　for　this　phenomenon　is　that　Naftifine　inhibits　STX　biosynthesis　and　improves　membrane　permeability.　Taken　together,　we　identified　STX　as　a　limiting　factor　of　PACT　in　S.　aureus.　Meanwhile,　we　found　that　the　combination　of　PACT　and　Naftifine,　an　inhibitor　of　STX　biosynthesis,　has　synergistic　antibacterial　effect　on　S.　aureus,　and　provide　a　new　way　for　the　rapid　and　efficient　treatment　of　S.　aureus　infection　without　drug　resistance.