The　identification　of　novel　and　efficient　piezoelectric　catalysts　is　crucial　for　practical　applications.　Utilizing　Density　Functional　Theory　(DFT)　calculations,　ZnIn2S4　(ZIS),　possessing　a　non-central　symmetric　crystal　structure,　is　identified　as　a　promising　piezoelectric　material　for　piezocatalysis.　Hierarchical　ZIS　nanosheets　are　synthesized　through　a　facile　hydrothermal　method,　and　defect　engineering　is　employed　to　enhance　their　activity.　By　optimizing　the　defect　concentration,　ZIS-300,　with　the　optimal　defect　level,　demonstrates　the　highest　H2　production　rate　of　approximately　3164.67　µmo1.g−1.h−1　under　ultrasound,　surpassing　previously　reported　piezocatalysts.　Furthermore,　ZIS-300　exhibits　good　stability,　maintaining　its　activity　and　structural　integrity　after　five　cycles.　Detailed　piezo-electrochemical　analyses　attribute　the　enhanced　piezocatalytic　performance　to　the　introduction　of　sulfur　vacancies,　which　create　a　shallow　donor　band　facilitating　the　generation　and　separation　of　charge　carrier.　This　work　contributes　to　a　deeper　understanding　of　designing　high-performance　piezocatalysts　through　theoretical　calculations　and　defect　engineering　strategies.　©　2025　Elsevier　B.V.