Large bone defect healing remains a challenge in current clinical treatment, which suggests the need for functional bone repair materials. Piezoelectric materials can generate electrical stimulation under mechanical stress to improve the tissue healing environment, which are emerging candidates for tissue engineering. We created a self-powered piezoelectric hydrogel by simply blending the zinc oxide (ZnO) nanoparticles and regenerating silk fibroin (RSF). Our piezoelectric hydrogel showed controllable and suitable mechanical and piezoelectric properties which could generate electrical stimulation to promote bone tissue healing. Incorporating ZnO into RSF hydrogels not only enhanced their mechanical properties by 1.7 times and increased piezoelectric output by 2.8 times, but also mitigated the degradation rate. In vitro experiments showed that piezoelectric hydrogels significantly promoted osteogenesis differentiation of bone marrow mesenchymal stem cells (BMSCs) and enhanced vascular network reconstitution. In vivo experiments verified the osteogenic and angiogenic potential of ZnO/RSF piezoelectric hydrogels. ZnO/RSF piezoelectric hydrogel, a simple but universal strategy of RSF-based material to generate electric currents by body movement, provides novel insights into the applications of piezoelectric hydrogel. STATEMENT OF SIGNIFICANCE: ZnO/RSF hydrogels with stable piezoelectric properties were prepared by doping ZnO, which can generate stable and continuous electrical signals under pressure. After implantation into the bone defect site, it can promote the osteogenic differentiation of bone marrow mesenchymal stem cells and improve the vasculogenic ability of human umbilical vein endothelial cells, thus promoting the healing of bone tissue.