It　remains　a　challenge　to　use　a　single　probe　to　simultaneously　detect　extracellular　pH　fluctuations　and　specifically　recognize　cancer　cells　for　precise　drug　delivery.　Here,　we　engineered　a　tetrahedral　framework　nucleic　acid-based　logic　nanoprobe　(isgc8-tFNA)　on　live　cell　membranes　for　simultaneously　monitoring　extracellular　pH　and　targeted　drug　delivery.　Isgc8-tFNA　was　anchored　stably　on　the　cell　surface　through　three　cholesterol　molecules　inserting　into　the　bilayer　of　the　cell　membrane.　Once　responding　to　the　acidic　tumor　microenvironment,　isgc8-tFNA　formed　an　i-motif　structure,　leading　to　turn-on　FRET　signals　for　monitoring　changes　of　extracellular　pH.　The　nanoprobe　exhibited　a　narrow　pH-response　window　and　excellent　reversibility.　Moreover,　the　nanoprobe　could　execute　logic　identification　on　the　cell　surface　for　precise　drug　delivery.　Only　if　both　in　the　acidic　microenvironment　and　aptamer-targeting　marker　are　present　on　the　cell　surface,　the　sgc8-ASO-chimera　strand,　carrying　an　antisense　oligonucleotide　drug,　was　released　from　the　nanoprobe　and　entered　into　targeted　cancer　cells　for　gene　silence.　Additionally,　the　in　situ　drug　release　facilitated　the　uptake　of　drugs　mediated　by　the　interaction　between　sgc8　aptamer　and　membrane　proteins,　resulting　in　enhanced　inhibition　of　cancer　cell　migration　and　proliferation.　This　logic　nanoprobe　will　provide　inspiration　for　designing　smart　devices　for　diagnosis　of　pH-related　diseases　and　targeted　drug　delivery.　©　2024　American　Chemical　Society.