A preliminary study for advanced HIFU therapy system was performed which enabled echographic marking and enhancing of the ultrasonic energy absorption efficiency at site of interest. As a main component of this system, we are developing phase change nano-droplet, a liquid precursor of a microbubble that changes into a bubble upon applying ultrasonic pulses. In this study, we investigated the effect of nano-droplet in temperature rise induced by HIFU exposure using gel phantom. It was found that HIFU exposure to nano-droplet suspended in Polyacrylamide gel resulted in approximately 2.5 times greater temperature elevation when nano-droplet concentration was more than 10 μM. The concentration was in the same order as concentration required for the generation of echographycally significant microbubbles. Also, it was suggested that not the droplet itself but the induced microbubble by the phase change pulse is responsible for the enhancement of the temperature elevation. Such results were promising for the potential effectiveness of our approach for the site-specific HIFU.