In this work, a novel electrochemical assay was constructed based on acid-induced dissolution of nanoparticles to trigger enzyme-free cleavage for thrombin (TB) detection. First, the magnetic bioconjugates Fe3O4/Au/s1 could link with ZnO/Au/TBA bioconjugates via complementary base pairing. Once target TB was introduced in this system to react with thrombin binding aptamer (TBA), the formed ZnO/Au/TBA/TB biocomplex could separate from Fe3O4/Au/s1 bioconjugates which could be removed by magnetic separation and further dissolved by acidolysis to turn ZnO nanoparticles (ZnO NPs) into Zn2+. Finally, the released Zn2+ was adopted into the modified electrode and cleaved the substrate sequence of the Zn2+-dependent DNAzyme, resulting in the removing of labeled ferrocene (Fc) and the decrease of electrochemical signal. In this way, the target TB detection is transferred to monitor large numbers of DNA fragments labeled with Fc cleaved by Zn2+-dependent DNAzymes, resulting in hundreds of thousands-fold amplification effect, further realizing the sensitive detection of TB. And the proposed electrochemical assay exhibited good sensitivity with the detection limit of 8.6 fM in a desirable dynamic range from 0.01 pM to 10 nM. With such design, this proposed electrochemical approach based on acid-induced dissolution of nanoparticles to trigger enzyme-free cleavage provides a simple and sensitive method for detection of other analysts. (C) 2018 The Electrochemical Society.