Abstract Ultrasound-mediated microbubble cavitation lithotripsy as a new minimally invasive approach has received great attention for the treatment of urinary stones. However, the attenuation of ultrasonic waves in human tissues and stone displacement during lithotripsy are two key issues limiting the development of this technology. In this paper, a method of interventional ultrasound-mediated microbubble cavitation lithotripsy is proposed, which can realize the in-situ delivery of ultrasonic waves and microbubbles. A piezoelectric ultrasound transducer with the center frequency of 461 kHz and output peak to peak acoustic pressures of 3.2 MPa is fabricated, and microbubbles with the concentration of 1.33×109/ml are synthesized. An extracorporeal experiment platform is built and in vitro tests of ultrasound mediated microbubble cavitation lithotripsy are conducted by using microbubbles with different concentrations and water. The results show that the proposed interventional ultrasound-mediated microbubble cavitation lithotripsy is an efficient method for the fragmentation of ureteral stones. The maximum mass reduction of the stone is 9.4 mg within 30 minutes of treatment under the combined action of ultrasound with the peak-negative pressure of 1.6 MPa and center frequency of 461 kHz and microbubbles with the concentration of 3.325×107/ml. The research results will provide a technical basis for further optimization of subsequent tentative schemes, in vivo experiments with animals and future clinical applications.