Even　though　black　phosphorus　(BP)　has　exhibited　outstanding　capabilities　in　biomedical,　physical,　and　energy　fields,　the　issues　of　degradation　under　ambient　conditions　and　unreactive　functional　interface　limit　its　further　application.　There　are　numerous　methodologies　utilized　to　prevent　BP　degradation;　however,　these　methods　usually　generate　further　problems　and　normally　do　not　involve　alterations　to　the　chemically　inert　BP.　Herein,　for　the　first　time,　we　propose　a　simple　and　efficient　strategy　to　prepare　and　modify　BP　nanosheets　(p-BPNSs)　by　employing　aromatic　1-pyrenylbutyric　acid　through　a　noncovalent　π-π　stacking　interaction.　This　strategy　not　only　adopts　a　novel　strategy　for　enhancing　the　stability　of　BPNSs　but　also　paves　a　convenient　way　to　anchor　other　active　biomolecules　such　as　a　targeting　effect　to　extend　the　biomedical　applications　of　BPNSs.　The　modified　p-BPNSs　exhibit　enhanced　physical　and　chemical　stabilities　as　well　as　rich　carboxyl　groups　for　further　modification.　In　this　work,　RGD-modified　p-BPNSs　exhibit　targeted　photothermal　therapy　ability　against　cancer　in　both　in　vitro　and　in　vivo　studies,　owing　to　anchoring　of　arginine-glycine-aspartic　acid　(RGD)　tripeptides,　which　could　target　nanosheets　into　the　tumor　site　through　systematic　circulation.　Consequently,　this　work　not　only　provides　a　new　concept　for　modifying　and　protecting　the　BP　but　also　opens　a　novel　window　for　extending　the　biomedical　application　of　BP　by　surface　engineering.　©　2019　American　Chemical　Society.