While the hepatocyte apoptosis induced by TiO2 nanoparticules (NPs) has been demonstrated, very little is known about the molecular mechanisms underlying this mouse liver apoptosis. In order to understand the hepatocyte apoptosis induced by intragastric administration of TiO2 NPs for consecutive 60 days, the hepatocyte apoptosis, various oxidative stress parameters and the stress-related gene expression levels were assayed for the mouse liver. 60 days of TiO2 NPs exposure, hepatocyte apoptosis in the liver could be observed, which was followed by increased reactive oxygen species accumulation, and decreased the stress-related gene expression levels of superoxide dismutase, catalase, glutathione peroxidase, metallothionein, heat shock protein 70, glutathione S transferase, P53, and transferrin; and the significant enhancement of the cytochrome p450 1A expression level. It implied that hepatocyte apoptosis, oxidative stresses, and alteration of expression levels of the genes related with TiO2 NPs detoxification/metabolism regulation and radical scavenging action. Therefore, the application of TiO2 NPs and exposure effects especially on human liver for long-term and low-dose treatment should be cautious. (C) 2010 Elsevier B.V. All rights reserved.