The applications of silica-based nanomaterials in dental fields as multifunctional scaffolds and carriers have been widely documented in recent years. However, toxicity of this type of nanoparticles in dental cells has not been elucidated in detail. The aim of present study was to investigate the effects of naked and PEGylated silica nanoparticles on cementoblasts. Methods including MTT assay, apoptosis, LDH, as well as ROS analysis were introduced in our study. Moreover, ALP analysis and alizarin red staining were additionally performed to indicate the influence of SiO2 and PEG-SiO2 on cementoblast differentiation. Results obtained from our designs and experiments demonstrated that naked silica nanoparticles could induce more cell toxicity than PEG-SiO2 nanoparticles, indicating PEGylation could efficiently reduce in vitro toxicity from several sections including ROS, LDH, and other important routes. Based on above results, we concluded that it was so necessary to process PEGylation while silica-based materials were applied in biomedicine and related fields including dental area.