Titanium dioxide (TiO_2) is known as sonocatalyst which generate hydroxyl radicals when the ultrasonic (US) is irradiated to TiO_2 (TiO_2/ US method). In this study, we investigated the cell damage effect and antitumor effect by the combination of ultrasonic irradiation and TiO_2 nanoparticles that is modified with preSl/S2 protein for targeting HepG2 cells. For irradiating of US to the preS1/S2-TiO_2 nanoparticles incorporated HepG2, cell injuring efficiency was evaluated by Trypan blue dye exclusion test. As a result, the cytostatic activity was acquired when irradiated at 1MHz, 0.1 W/ cm^2, 30 second, 50% duty in the presence of TiO_2 nanoparticle modified with preS1/S2 protein. This cytostatic activity was observed at 24 hour after US irradiation, and this effect was significantly enhanced as time elapsed. Also, antitumor effect by TiO_2 / U.S. method in vivo was evaluated. When ultrasonic irradiation was performed by the frequency of 3 times per week, and the irradiation conditions of 1 MHz, 1 W/cm^2, 1 min, no significant damages to the mice was ovserved. These irradiation condition revealed the antitumor effect significantly. Moreover the further research, such as the examination of the irradiation conditions of ultrasound, injection amount of TiO_2 nanoparticles and the specific binding ability to HepG2 tumor after i.v. injection, are proposed.