Abstract: A multi-focus histotripsy method based on a pulsed ultrasound phased array with hundred elements is provided. Excitation amplitude and phase of individual elements are regulated to control a phased array to produce multiple focus modes. A two-stage histotripsy is performed based on these focus modes. In a first stage, a first pulsed ultrasound is applied to an experimental sample in a target area to induce generation of cavitation microbubbles and boiling bubbles to preliminarily homogenize the experimental sample to form a loose product; and in a second stage, the experimental sample is mechanically disrupted and homogenized using a second pulsed ultrasound. The first pulsed ultrasound and the second pulsed ultrasound each are a hundred micro-second pulse or a milli-second pulse. Duty cycles of the first pulsed ultrasound and the second pulsed ultrasound are 3-10% and less than 2%, respectively. A multi-focus histotripsy system is further provided.