A　functionalized　Fe3O4@Ag　magnetic　nanoparticle　(NP)　biosensor　for　microRNA　(miRNA)　capture　and　ultrasensitive　detection　in　total　RNA　extract　from　cancer　cells　was　reported　in　this　paper.　Herein,　Raman　tags-DNA　probes　modified　Fe3O4@Ag　NPs　were　designed　both　as　surface-enhanced　Raman　scattering　(SERS)　SERS　and　duplex-specific　nuclease　signal　amplification　(DSNSA)　platform.　Firstly,　target　miRNAs　were　captured　to　the　surface　of　Fe3O4@Ag　NPs　through　DNA/RNA　hybridization.　In　the　presence　of　endonuclease　duplex　specific　nuclease　(DSN),　one　target　miRNA　molecule　could　rehybrid　thousands　of　DNA　probes　to　trigger　the　signal-amplifying　recycling.　Base　on　the　superparamagnetic　of　Fe3O4@Ag　NPs,　target　miRNA　let-7b　can　be　captured,　concentrated　and　direct　quantified　within　a　PE　tube　without　any　PCR　preamplification　treatment.　The　detection　limit　was　0.3　fM　(15　zeptomole,　50　mu　L),　nearly　3　orders　of　magnitude　lower　than　conventional　fluorescence　based　DSN　biosensors　for　miRNA(similar　to　100　fM),　even　single-base　difference　between　the　let-7　family　members　can　be　discriminated.　The　result　provides　a　novel　proposal　to　combine　the　perfect　single-base　recognition　and　signal-amplifying　ability　of　the　endonuclease　DSN　with　cost-effective　SERS　strategy　for　miRNA　point-of-care　(POC)　clinical　diagnostics.　(C)　2015　Elsevier　B.V.　All　rights　reserved.