An ultrasonic-assisted method to directly prepare nanocrystalline TiO2 has been used. TiO2 was synthesized by the hydrolysis of Tetraisopropyl titanate (TIPT) in the presence of de-ionized water and ethanol under high-intensity ultrasonic irradiation (24 KHz, 300 W/cm2) at different conditions. The effect of water content, water-to-TIPT ratio, water-to-ethanol ratio and sonication time on the particle size of TiO2 has been investigated by using design of experiment (DOE). The water content, water-to-TIPT ratio, water-to-ethanol ratio and sonication time were varied in the range 100-150 ml, 50-75 v/v, 20-30 v/v and 3-4 hr, respectively. Particle size of TiO2 was characterized using particle size analyzer. The results of DOE show that water content has the greatest effect on the particle size of TiO2