High-performance photocatalytic H2 evolution materials require strong light absorption capability, excellent photogenerated charge separation ability and efficient charge carrier migration capability. In this study, we designed a piezoelectric photocatalytic heterojunction composed of UiO-66-NH2 and ZnIn2S4 nanosheets with sulfur vacancies. The Sv-UZ-45 heterojunction achieved piezoelectric photocatalytic H2 evolution performance of 3886.4 μmol·g-1·h-1, with a 4.6 times enhancement due to the synergistic effect of piezoelectric effect and defect engineering. The introduction of sulfur vacancies enables the heterojunction to obtain stronger light absorption, while the higher CB position of rich-sulfur vacancies ZnIn2S4 is more favorable for the photocatalytic reduction reaction. In addition, the heterojunction with rich-sulfur vacancies exhibits a stronger piezoelectric effect than without vacancies, thus providing a powerful driving force for the separation of photogenerated charge carriers. Finally, ESR was used to explain the potential photocatalytic mechanism and showed that Sv-UZ-45 adheres to the Z-scheme carrier migration pathway. This work elucidates the synergistic interaction between piezoelectric effect and defect engineering, providing new insights for the further development of high-performance piezoelectric photocatalysts.