The activation of immune-stimulatory molecules is critical for effective antitumor immunotherapy. Mechanical high-intensity focused ultrasound (mHIFU) sustains this activation in tumor cell debris through cavitation. To enhance cavitation, perfluorohexane nanodroplets (NDs-PFH) were utilized in this study to lower the cavitation threshold during mHIFU ablation. Our results showed that NDs-PFH combined with mHIFU induced 77.2 % Hepa 1-6 tumor cells death, and activated the release of damage-associated molecular patterns (such as HMGB1, CRT, and ATP), enhancing dendritic cell maturation (20.2 %) and T cell activation (1.8 % of TNF-α