Differentially expressed proteins in mouse liver caused by toxicity of titanium nanoparticles ($TiO_2$ NPs) were screened. More than 1,400 protein spots in mouse liver were detected by twodimensional gel electrophoresis, and 15 proteins that showed greater than 2-fold expressional changes in response to $TiO_2$ NPs were identified by liquid chromatography-tandem mass spectrometry. Of these, 12 proteins were down-regulated and 3 proteins were up-regulated upon treatment with $TiO_2$ NPs. The 15 differentially expressed proteins could be used for detection of inflammation, apoptosis, and antioxidative reaction for treatment of acute hepatic damage by $TiO_2$ NPs.