Single-atom　catalysts　(SACs),　a　newcomer　in　the　field　of　nanocatalysis,　have　sparked　tremendous　interest　thanks　to　their　high　atomic　utilization,　unsaturated　coordination　environment,　and　attractive　properties.　Unfavorably,　few　studies　have　focused　on　the　applications　of　the　SACs　in　the　biosensors.　Herein,　a　reliable　SiO2-templated　strategy　was　elaborately　designed　to　synthesize　single-atom　platinum　anchored　on　the　surface　of　hollow　cadmium　sulfide　(HCdS–Pt1).　Experimental　results　and　density　functional　theory　(DFT)　calculation　showed　that　the　introduction　of　Pt1　was　helpful　for　carrier　separation　and　allowed　high　carrier　density.　As　a　proof-of-concept,　HCdS–Pt1　was　served　as　a　photoelectrochemical　sensing　platform　to　detect　biomolecules.　To　construct　such　a　universal　single-atom　biosensor,　horseradish　peroxidase　(HRP)　and　glucose　oxidase　(GOx)　were　encapsulated　into　DNA　flowers　(HRP&GOx-DF)　with　the　high　biorecognition　capability.　The　as-prepared　HRP　&GOx-DFs　could　not　only　improve　the　thermal　stability　of　the　enzyme　but　also　serve　as　the　versatile　recognition　elements.　In　our　design,　HRP&GOx-DFs,　enriched　by　target　analyte,　would　bioetch　HCdS–Pt1　irreversibly,　thus　resulting　in　the　change　of　the　electrical　readout.　Expectedly,　SACs,　combined　with　DNA　nanotechnology,　opens　new　opportunities　for　protein　diagnostics　and　biosecurity.　©　2020　Elsevier　Ltd