Abstract: Liver cancer is one of the leading causes of cancer-related deaths worldwide. However, all liver cancer treatment options currently available fail to achieve a complete cure. Recently, research on pyroptosis has attracted significant attention from researchers in the field of cancer therapy. Pyroptosis is an inflammatory cell death closely related to oxidative stress caused by reactive oxygen species (ROS). The induction of pyroptosis can lead to the inhibition of tumor proliferation and the improvement of tumor immune responsiveness and is considered a novel therapeutic mechanism that can be utilized to develop new cancer therapies. Sonodynamic therapy (SDT), which involves a synergistic application of sonosensitizers and low-intensity focused ultrasound to generate cytotoxic ROS, demonstrates certain advantages and potentials in the treatment of liver cancer. However, liver cancer treatment utilizing SDT is still in the stage of preclinical research, and the specific conditions of ultrasound treatment, the biological effects, and the mechanisms of action are not fully understood. In this review, we discussed the potential of utilizing pyroptosis in liver cancer treatment, the mechanism of cancer therapy with ROS generated by SDT, and the latest findings concerning SDT from clinical and basic research. We discussed the utilization of SDT to force the accumulation of ROS in tumors to exceed the cytotoxicity threshold. Thus, SDT promotes pyroptosis and enhances the immune response to cancer. Furthermore, we discussed the prospects for applying the mechanism of SDT-induced pyroptosis in cancer therapy, thereby providing a better theoretical and experimental foundation for the clinical translation of SDT for liver cancer treatment.