Detection　of　intracellular　miRNAs,　especially　sensitive　imaging　of　in　vivo　miRNAs,　is　vital　to　the　precise　prediction　and　timely　prevention　of　tumorgenesis　but　remains　a　technical　challenge　in　terms　of　nuclease　resistance　and　signal　amplification.　Here,　we　demonstrate　a　gold　nanoparticle-based　spherical　nucleic　acid-mediated　spatial　matching-guided　nonenzymatic　DNA　circuit　(SSDC)　for　efficient　screening　of　intracellular　miRNAs　and,　in　turn,　finding　cancerous　tissues　in　living　organisms　before　the　appearance　of　clinical　symptoms.　Due　to　the　substantially　enhanced　nuclease　resistance,　the　false　positive　signal　is　avoided　even　in　a　complex　biological　medium.　Target　miRNA　can　straighten　out　the　hairpin　DNA　probe　to　be　linear,　allowing　the　probe　to　penetrate　into　the　internal　region　of　a　core/shell　DNA-functionalized　signal　nanoampfilier　and　initiate　a　strand　displacement　reaction,　generating　an　amplified　fluorescence　signal.　The　detection　limit　is　as　low　as　17　pM,　and　miRNA　imaging　is　in　good　accordance　with　the　gold　standard　polymerase　chain　reaction　method.　The　ability　to　image　intracellular　miRNAs　is　substantially　superior　to　that　of　conventional　fluorescence　in　situ　hybridization　techniques,　making　in　vivo　SSDC-based　imaging　competent　for　the　precise　prediction　of　tumorigenesis.　By　intratumoral　chemotherapy　guided　by　SSDC-based　imaging,　tumorigenesis　and　progression　are　efficiently　controlled　before　the　onset　of　clinical　symptoms.　©　2024　American　Chemical　Society.