ABSTRACT Objective To prepare a near infrared fluorescent multifunctional nano particle, and to evaluate its in vitro ultrasound, photoacoustic imaging ability and the effect of ablation of bovine liver with high intensity focused ultrasound (HIFU), and to explore the mechanism of its synergistic effect on HIFU through cavitation detection.Methods IR780 and PFH coloaded?lipid?nanoparticles (IR780-CLs)?were prepared using film-ultrasonic?method,the structural characteristics of nanoparticles were observed by transmission electron microscopy, the particle size and potential of nanoparticles were detected by multi angle particle size analysis and Zeta potentiometers, and encapsulation efficiency of IR780 was detected by ultraviolet spectrophotometer. The effect of ultrasound and photoacoustic imaging were observed in vitro,in vitro bovine liver experiment was used to evaluate the synergistic effect of IR780-CLs on HIFU in vitro, and through passive cavitation detection, the change curve of root mean square (RMS) of broadband noise signal amplitude with time was taken to reflect real-time cavitation signal.Results The synthesized IR780-CLs nanoparticles were spherical and uniform, with an average surface potential of (34.5 ± 3.2) mV and diameter of (246.5 ± 12.4) nm, and encapsulation efficiency of IR780 was 88%. IR780 CLs nanoparticles had good ultrasound and photoacoustic imaging effects in vitro. There was a good linear relationship between photoacoustic signal intensity and concentration of nanoparticles. In vitro bovine liver experiment showed that it had a significant synergistic effect on HIFU. Passive cavitation detection further verified that the RMS value of cavitation signal in IR780-CLs group was higher than that in PBS group.Conclusion In this experiment, multifunctional nano particles IR780-CLs were successfully prepared, which have good ultrasound and photoacoustic imaging capabilities, and can significantly improve the efficiency of HIFU ablation of bovine liver. Cavitation effect is the main mechanism of enhancing the efficiency of HIFU.