Recently　reported　black　phosphorus　quantum　dots　(BPQDs)　possess　unique　photocatalysis　activities.　However,　the　environmental　instability　accompanied　by　a　hypoxic　tumor　microenvironment　(TME)　seriously　hindered　the　bioapplications　of　BPQDs,　especially　in　oxygen-dependent　photodynamic　therapy　(PDT).　Here,　we　construct　a　hepatocellular　carcinoma　(HCC)-specific　targeting　aptamer　＂TLS11a＂-decorated　BPQDs-hybridized　nanocatalyst,　which　can　specifically　target　HCC　tumor　cells　and　self-compensate　oxygen　(O　2　)　into　hypoxic　TME　for　enhancing　PDT　efficiency.　The　BPQD-hybridized　mesoporous　silica　framework　(BMSF)　with　in　situ　synthesized　Pt　nanoparticles　(PtNPs)　in　the　BMSF　is　simply　prepared.　After　being　decorated　by　TLS11a　aptamer/Mal-PEG-NHS,　the　resultant　nanosystem　(refer　as　Apt-BMSF@Pt)　exhibits　excellent　environmental　stability,　active　targeting　ability　to　HCC　cells,　and　self-compensation　ability　of　oxygen.　Compared　with　the　PEG-BMSF@Pt　without　H　2　O　2　incubation,　the　PEG-BMSF@Pt　nanocatalyst　exhibits　4.2-folds　O　2　and　1.6-folds　1　O　2　generation　ability　in　a　mimetic　closed-system　in　the　presence　of　both　H　2　O　2　and　near-infrared　laser.　In　a　mouse　model,　the　Apt-BMSF@Pt　can　effectively　accumulate　into　tumor　sites,　and　the　core　of　BMSF　subsequently　can　act　as　a　photosensitizer　to　generate　reactive　oxygen　species,　while　the　PtNPs　can　serve　as　a　catalyst　to　convert　H　2　O　2　into　O　2　for　enhancing　PDT　through　self-compensation　mechanisms　in　hypoxic　TME.　By　comparison　of　the　tumor　volume/weight,　H&E,　and　immunohistochemical　analysis,　the　excellent　antitumor　effects　with　minimized　side　effects　of　our　Apt-BMSF@Pt　could　be　demonstrated　in　vivo.　Taken　together,　the　current　study　suggests　that　our　Apt-BMSF@Pt　could　act　as　an　active　targeting　nanocatalyst　for　programmable　killing　of　cancer　cells　in　hypoxic　TME.　©　2019　American　Chemical　Society.