Objective investigate the cavitation activity and postoperative pathological changes of rabbit liver after lipid nano-fluorocarbon droplets enhanced HIFU ablation. Methods Perfluoropentane lipid nanofluorocarbon droplets (L-PFP) were prepared. Then 24 normal New Zealand rabbits were randomly divided into control group (HIFU group) and L-PFP group. The rabbit liver was ablated by HIFU under the guidance of B-ultrasound (Ultrasonic energy: 900 J). The passive cavitation detection system (PCD) is used to monitor cavitation activities. H&E staining was performed on rabbit liver samples immediately after ablation, 1d, 3d and 7d, respectively, to observe the pathological changes in the process of ablation. Results After the injection of L-PFP through auricular vein, the cavitation bubbles in HIFU irradiated rabbit liver were more obvious. The gray level change value was 1.93 times that of the control group, and the cumulative transient cavitation dose was 6.3 times that of the control group. Gross pathology and H&E results showed that l-PFP group caused severe tissue damage, more complete cell degeneration and more intense inflammatory response. In the HIFU group, 7d ablation was used to repair normal tissues, and the time required for recovery was significantly shorter than that in the L-PFP group. Conclusion Lipid nano-fluorocarbon droplets can effectively improve the ablation effect of HIFU by enhancing the cavitation effect and prolonging the time required for the ablation.