Abstract: Objective: To investigate the synergistic effect of high-intensity focused ultrasound (HIFU) combined with perfluoropentane droplets (PFP) on the treatment of mouse breast cancer 4T1 cells. Methods: PFP were prepared and their average particle size and morphology were examined. Three groups were set up in the experiment: blank control group, HIFU treatment group, HIFU combined with PFP treatment group, and the ability of HIFU combined with PFP for increasing the efficacy of 4T1 cells therapy in vitro was detected by flow cytometry; B-mode ultrasound was used to observe the gray changes before and after HIFU ablation and the percentage of perfusion defect in contrast-enhanced ultrasound to evaluate the synergistic ablation ability of HIFU combined with PFP for subcutaneously transplanted tumors in nude mice. Results: The average particle size of the prepared PFP was 1.2 μm, and the shape was regular spherical. Cell tests showed that 4T1 cells mortality (23.50 ±1.34)% in the HIFU combined with PFP treatment group was significantly higher than that in the HIFU-treated group alone (14.34 ±0.55)% and that in the HIFU sham group (11.76 ±0.62)%, (P <0.05). Animal experiments showed that the percentage of tumor necrotic area in the HIFU combined with PFP treatment group (84.03 ±4.47)% was significantly higher than that in the HIFU treatment group alone (41.23 ±4.24)%, (P <0.05), there was no obvious perfusion defect in the blank control group. Conclusion: HIFU combined with PFP can significantly enhance the ablation ability of breast cancer cells and tissues.