In　this　study,　a　biosensing　system　based　on　nicking-enhanced　rolling　circle　amplification　(N-RCA)　was　proposed　for　the　highly　sensitive　detection　of　cancer-related　let-7a　microRNA　(miRNA).　The　sensing　system　consists　of　a　padlock　probe　(PP),　which　contains　a　target　recognition　sequence　and　two　binding　sites　for　nicking　endonuclease　(NEase),　and　molecular　beacon　(MB)　as　reporting　molecule.　Upon　hybridization　with　let-7a,　the　PP　can　be　circularized　by　ligase.　Then,　the　miRNA　acted　as　polymerization　primer　to　initiate　rolling　circle　amplification　(RCA).　With　the　assistance　of　NEase,　RCA　products　can　be　nicked　on　the　cyclized　PP　and　are　displaced　during　the　subsequent　duplication　process,　generating　numerous　nicked　fragments　(NFs).　These　NFs　not　only　induce　another　RCA　reaction　but　also　open　the　molecular　beacons　(MBs)　via　hybridization,　leading　to　significantly　amplified　fluorescence　signal.　Under　the　optimized　conditions,　this　method　exhibits　high　sensitivity　toward　target　miRNA　let-7a　with　a　detection　limit　of　as　low　as　10 pM,　a　dynamic　range　of　three　orders　of　magnitude　is　achieved,　and　its　family　member　is　easily　distinguished　even　with　only　one　mismatched　base.　Meanwhile,　it　displays　good　recovery　and　satisfactory　reproducibility　in　fetal　bovine　serum　(FBS).　Therefore,　these　merits　endow　the　newly　proposed　N-RCA　strategy　with　powerful　implications　for　miRNA　detection.　[Figure　not　available:　see　fulltext.].　©　2018,　Springer-Verlag　GmbH　Germany,　part　of　Springer　Nature.