Lead　poisoning　endangers　soil,　plants　and　human　health　due　to　its　toxic　effect.　It　is　urgent　to　develop　ideal　tool　for　the　in　vivo　detection　of　Pb2+.In　this　study,　tetrahedron-based　Pb2+-sensitive　DNAzyme　sensor　(TPS)　is　constructed　by　taking　advantages　of　a　classic　Pb2+-dependent　GR-5　DNAzyme　and　DNA　tetrahedral　structure,　where　the　cleavage　substrate　and　DNAzyme　are　modified　with　fluorophore　FAM　and　quencher　BHQ-1,　respectively.　DNA　tetrahedron　is　arranged　at　the　terminus　of　substrate/DNAzyme　duplex　to　offer　the　protective　shield　against　the　nuclease　attack.　In　the　absence　of　Pb2+,　FAM　and　BHQ-1　are　kept　close　and　FAM　fluorescence　is　efficiently　quenched.　However,　in　the　presence　of　Pb2+　cofactor,　the　DNAzyme　exhibits　the　catalytic　activity　and　cleaves　the　substrate　strands,　spatially　separating　the　FAM　away　from　BHQ-1　and　releasing　fluorescence.　Utilizing　the　sensing　probe,　the　Pb2+　can　be　quantitatively　detected　down　to　1　nM　without　the　interference　from　nontarget　metal　ions.　Even　if　incubating　in　the　human　serum　solution　for　12　h,　no　substantial　nuclease　degradation　is　detected.　In　different　complex　biological　milieu,　the　TPS　can　preserve　the　85%　of　fluorescence　signal,　indicating　that　the　developed　TPS　is　a　promising　tool　for　the　future　application　in　the　in　vivo　detection　of　Pb2+.