The aim of this study is to compare the cyto and genotoxic effects of TiO2 and TiSiO4 nanoparticles on human embryonic kidney cells (HEK-293). The cell viability, induction of oxidative stress, and cell apoptosis induction were assessed after 48 h of cell exposure to TiO2 and TiSiO4 nanoparticles separately. Our results showed that nanoparticles induce the generation of reactive oxygen species (ROS) followed by significant depletion of glutathione levels and increased lipid peroxidation. The cells exhibited apoptotic morphology like condensed chromatin and nuclear fragmentation after 48 h of treatment. Both the particles induce oxidative stress and DNA damage in a dose dependent manner. Oxidative stress is the underlying mechanism by which nanoparticle causes DNA damage and apoptosis. This study further indicate that TiO2 nanoparticles has more toxic effects than TiSiO4 nanoparticles on HEK cells, which demonstrate that larger size may be responsible for retardant of cellular uptake. This might be reducing the toxicity of TiSiO4 nanoparticles.