Although HIFU therapy is very low invasive method for tumor treatment, its time inefficiency and the absence of focus detecting mechanism of current systems limit the number of applicable cases. For an improved HIFU tumor treatment system, we propose to utilize a non-echogenic liquid nanodroplet which turns into highly echogenic microbubbles upon non-therapeutic ultrasound pulses. Such a nanodroplet would give echographic information on the focus of HIFU when exposed to the pulse and accelerate HIFU treatment by enhancing the ultrasonic energy deposition as microbubble. As such a nanoparticle system, we developed a phase change nanodroplet (PCND) which consists of superheated perfluorocarbon nanodroplet coated with PEGylated phospholipids. Significance of PCND to enhance ultrasonically induced therapeutic effects was investigated on mice, rats, and rabbits. At frequencies of 2 and 3 MHz, it was found that the presence of PCND (and generated microbubbbles) halved the intensity threshold for inducing thermal damage. At frequency around 1 MHz, it was found that the PCND halved the threshold for inducing damage in murine tumor, and the damage was induced both by thermal and cavitational effects of ultrasound. [This work was in part entrusted by the New Energy and Industrial Technology Development Organization, Japan.]