Methods　based　on　electrochemical　biosensors　have　been　developed　for　detection　of　microRNA-21　(miRNA-21),　but　most　involve　complicated　labeling　or　stripping　procedures　and　are　unsuitable　for　routine　use　in　diagnosis/treatment　of　IgA-nephropathy.　Herein　we　report　on　the　proof-of-concept　of　simple　and　sensitive　potentiometric　DNA　biosensor　for　specific　detection　of　miRNA-21　coupling　and　catalytic　hairpin　assembly　(CHA)　with　target　recycling.　This　system　consists　of　two　hairpin　DNA　probes　and　one　single-stranded　DNA　(capture　probe).　To　decrease　the　background　signal,　the　thiolated　capture　probe　is　covalently　conjugated　onto　a　cleaned　gold　electrode　through　typical　Au-S　bond.　Upon　target　miRNA-21　introduction,　the　analyte　opens　hairpins　DNA　in　turn　to　propagate　the　CHA　reaction　between　two　alternating　hairpins　accompanying　the　release　of　target　miRNA-21　for　recycling,　thereby　resulting　in　formation　of　numerous　nicked　double-helixes.　Meanwhile,　the　newly　produced　CHA　product　hybridizes　with　the　immobilized　capture　DNA　probe　on　the　electrode,　thus　causing　the　change　in　the　surface　charge　density　for　potentiometric　measurement.　Under　optimum　conditions,　CHA-based　DNA　biosensor　presents　good　potentiometric　responses　for　determination　of　target　miRNA-21　at　a　level　as　low　as　43　fM.　An　intermediate　precision　of　＜10%　is　accomplished　with　the　batch-to-batch　identification.　The　specificity　and　stability　of　CHA-based　biosensor　are　satisfactory.　Importantly,　CHA-based　potentiometric　biosensor　offers　promise　for　the　label-free,　rapid,　simple,　cost-effective　analysis　of　biological　samples.　©　2018　Elsevier　B.V.