Surface-enhanced　Raman　scattering　(SERS)-based　biosensing　has　strong　potential　owing　to　its　high　sensitivity　and　good　selectivity.　In　this　study,　a　SERS　biosensing　platform　for　microRNA-21　detection　was　proposed　by　combining　heating-enhanced　duplex-specific　nuclease　(DSN)-assisted　target　recycling　amplification　and　silver　nanocube　(AgNC)-based　SERS　enhancement.　The　activity　of　DSN　was　greatly　enhanced　by　increasing　the　surface　temperature　of　a　heated　Au　electrode　(HAuE)　during　the　DSN-assisted　target　recycling　process,　resulting　in　dramatic　miRNA-21　amplification　detection.　4-Mercaptobenzoic　acid　(4-MBA)　acting　as　a　Raman　reporter　was　immobilized　onto　the　surface　of　AgNC　to　form　a　AgNC/4-MBA　SERS　tag　with　AgNC　providing　significantly　larger　electric　field　enhancement　and　thus　excellent　SERS　applications　compared　with　conventional　silver　or　gold　nanospheres.　This　enhancement　was　attributed　to　the　well-known　＇lighting　rod＇effect　derived　from　the　sharp　geometrical　feature　of　the　edges　and　corners　of　AgNCs.　These　factors　lead　to　the　high　sensitivity　of　the　proposed　SERS　biosensor　for　the　miRNA-21　measurement.　A　limit　of　detection　of　2.88　fM　(S/N　=　3)　was　achieved　at　an　electrode　temperature　of　55　°C,　which　was　decreased　by　more　than　three　magnitudes　compared　with　that　at　25　°C.　©