The damage of bovine serum albumin (BSA) molecules under ultrasonic irradiation in the presence of nano-sized silicon dioxide (SiO2) particles was studied by UV-Vis and fluorescence spectra. In addition, the influences of ultrasonic irradiation time, nano-sized SiO2 addition amount, solution acidity (pH) and ultrasonic irradiation power on the damage of BSA molecules in aqueous solution were also detected. For BSA solution of 1.0 10-5 mol·L-1 at (37.0±0.2) ℃, the UV-Vis spectra of BSA solutions showed that the absorption peaks of BSA displayed obvious hyperchromic effect with the increase in some influence factors such as ultrasonic irradiation time, nano-sized SiO2 addition amount, pH value and ultrasonic irradiation power. However, the fluorescence spectra of BSA solutions showed the phenomenon of fluorescence quenching with the increase in ultrasonic irradiation time, nano-sized SiO2 addition amount, pH value and ultrasonic irradiation power. Moreover, the possible mechanism behind the damage of BSA molecule in the presence of nano-sized SiO2 powders under ultrasonic irradiation was discussed. It was considered that the damage of BSA molecules was attributed to the formation of ·OH radicals resulting from the sonoluminescence and high-heat excitation of ultrasonic cavitation. The research results could be of great significance to using sonocatalytic method to treat tumour in clinic application and for developing nano-sized drug in the future.