Extensively　drug-resistant　Acinetobacter　baumannii　(XDR-AB)　has　raised　considerable　concerns　due　to　its　mortal　damage　to　humans　and　its　high　transmission　rate　of　infections　in　hospitals.　However,　current　antibiotics　not　only　show　poor　anti-infection　effects　in　vivo　but　also　frequently　cause　high　nephrotoxicity　and　neurotoxicity.　Herein,　we　report　a　near-infrared　(NIR)　light-initiated　antimicrobial　photodynamic　therapy　(aPDT)　to　effectively　treat　in　vivo　XDR-AB　infections　based　on　photosensitizer　(PS)　loaded　upconversion　nanoparticles　(UCNPs,　LiYF4:Yb/Er).　Such　nanoagents　feature　robust　NIR　triggered　UC　luminescence　and　high-efficiency　energy　transfer　from　UCNPs　to　the　loaded　PS,　thereby　allowing　NIR-triggered　generation　of　reactive　oxygen　species　(ROS)　for　destroying　the　bacterial　cell　membrane.　This　strategy　permits　a　high　antibacterial　activity　against　XDR-AB,　resulting　in　a　decline　of　4.72　log(10)　in　viability　at　a　dose　of　50　mu　g　mL(-1)　UCNPs-PVP-RB　with　980　nm　laser　irradiation　(1　W　cm(-2)).　More　significantly,　we　can　achieve　excellent　therapeutic　efficacy　against　deep-tissue　(about　5　mm)　XDR-AB　infections　without　causing　any　side　effects　in　the　murine　model.　In　brief,　such　NIR-activated　aPDT　may　open　up　new　avenues　for　treating　various　deep-tissue　intractable　infections.