The present study was carried out to investigate the impact of various concentrations of SiO2 nanoparticles (SiO2NP) on the commonly available freshwater fish Oreochromis mossambicus. The 96 h median lethal concentration (LC50) of SiO2 NP was found to be between 270−280ppm. This novel study has demonstrated histological alterations in the hepatic tissues and a dose-dependent depletion of tissue protein content and an elevated transaminases activity in the treated fish, which has facilitated understanding of the impact of SiO2 NP in O. mossambicus.