The development of high-performance solar-photocatalysts/sonocatalysts for overall water splitting production of H2 and H2O2 is highly significant to their energy and medical applications, but remains challenging. Herein, we have discovered that Bi2Te3 nanosheets have a piezoelectricity, and experimentally confirmed the ultrasound-driven indirect-to-direct bandgap semiconductor transition which enables ultrasound stimulation to reconstruct band structure in competent for sonophotocatalytic overall water splitting production of H2 and H2O2. Under the assistance/driving of a low-density pulsed ultrasound, the solar-photocatalysis of Bi2Te3-Au nanosheets achieves extrahigh H2 and H2O2 production efficiencies (29.7 mmol/g/h H2 and 14.6 mmol/g/h H2O2), which are far higher than that previously reported about overall water splitting. For medical application, we have proposed a sonocatalytic strategy of combining hydrogen therapy and sonodynamic therapy for treatment of deep tumors, achieving a high outcome of orthotopic liver tumor treatment with a 100 % mice survival rate and a 100 % tumor eradication rate. High sonophotocatalytic performance, high biosafety and high anti-cancer efficacy endow Bi2Te3-Au nanosheets with a great potential for green energy and medical applications. These findings will provide an inspiration for exploitation and utilization of the piezoelectricity and sonophotocatalysis of A2VB3VI semiconducting nanomaterials.