<p>In recent years, breakthrough progress has been made in tumor immunotherapy, which includes enhancing T-cell function. However, most approved indications exhibit response rates of only 10–25%. In this study, we attempted to use a novel low-intensity histotripsy (LIH) technique to mechanically ablate tumor tissues, induce the exposure of tumor antigens, and explore its synergistic effects on tumor debulking and antitumor immune responses. We constructed an MC38 mouse model containing the specific OVA_257-264 antigen to test the mechanical ablation effect of LIH on tumor tissues and the resulting antitumor immune response. The results of this study revealed that LIH resulted in significant mechanical damage to tumor tissues. Pathological and gross findings revealed that following LIH, the tumor tissues developed cavitary structures accompanied by inflammatory cell infiltration, and the tumor growth rate was significantly reduced. Moreover, the mechanical damage caused by LIH led to the release of damage-associated molecular patterns (DAMPs) and appeared to promote antigen presentation by dendritic cells (DCs), increasing the infiltration and activation of CD8 + T cells in tumors. This finding also indicated an antitumor immune response induction trend and may contribute to the inhibition of distant tumor growth. Collectively, these preliminary results reveal that LIH may represent a potentially complementary exploratory approach combined with antitumor immunotherapy.</p>