Catalytic　DNA　circuits　show　great　potential　for　precise　intracellular　imaging.　However,　their　selectivity　and　efficiency　are　often　hindered　by　low　anti-interference　performance　in　the　cytoplasm＇s　complex　environment.　Thus,　designing　DNA　circuits　that　exhibit　enhanced　stability　and　specific　activation　is　crucial　for　the　accurate　intracellular　biomolecule　imaging.　Herein,　we　proposed　a　framework　nucleic　acids　based　endogenously　activated　entropy-driven　catalytic　(EDC)　circuit,　FEED,　for　in　vivo　microRNA　imaging　with　enhanced　selectivity　and　efficiency.　To　mitigate　undesired　signal　leakage　before　reaching　the　target　cells,　the　dominating　EDC　circuitry　fuel　strand　was　initially　blocked　with　a　disulfide　bond　modified　DNA　strand,　and　the　target　recognition　site　of　sensing　module　was　also　closed　by　apurinic/apyrimidinic　(AP)　sites.　This　configuration　allowed　selective　activation　of　the　EDC　by　endogenous　GSH　and　human　apurinic/apyrimidinic　endonuclease　1　(APE1)　in　cancer　cells,　facilitating　high-contrast　miRNA　imaging.　Additionally,　the　integrating　a　distinctive　DNA　tetrahedral　structure　into　the　EDC　circuit　enhances　both　biostability　and　cellular　reaction　efficacy.　This　in-site　activation　FEED　circuit　offers　a　programmable　and　modular　amplification　strategy　for　biomarker　detection　in　live　cells　and　mice,　providing　a　potentially　valuable　molecular　tool　for　living　systems.　©　2024　Elsevier　B.V.