Single-phase ZnO nanoparticles were successfully prepared by solid-liquid reaction ball milling assisted by ultrasonic wave. The samples were characterized by X-ray diffraction and transmission electron microscopy. By the comparison of the as-milled products with and without the help of ultrasonic wave, it is found that ultrasonic wave is a key factor promoting the transformation from Zn(OH)(2) to ZnO. Based on hot-spot theory, the formation mechanism of the single-phase ZnO nanoparticles under ultrasonic wave assistance is determined.