A kind of experimental setup, named as UC-1500, was designed. SiO2 nanoparticles preparing by ultrasonic-mechanical method were studied, and the effects of ultrasound field, dispersant concentration and grinding time on grain-size and appearance of SiO2 nanoparticles were investigated. The results showed that the grain-size was smaller and the stability of SiO2 nanoparticles was better in ultrasonic field.The optimum values of such reaction factors as the space between two adjacent teeth of stirring rad, grinding time, dispersant concentration and the rotating speed of stirring rod were 15 mm, 9 h, 0.09 g·L -1 and 300 r·min -1 , respectively.With grinding time being the main factor, the effects of dispersant concentration, the rotating speed of stirring rod and the space between two adjacent teeth of stirring rod decreased successively.