In this study, the differentially expressed proteins by titanium dioxide nanoparticles ($TiO_2$ NPs) in mouse lung were examined via proteomic approach to better understand the molecular mechanism by which $TiO_2$ NPs could induce toxicities at the protein level. We identified eight proteins that exhibited more than two-fold changes in expression by $TiO_2$ NPs. Of these, five proteins, named cytoplasmic aconitase, L-lactate dehydrogenase A chain, carbonic anhydrase 1, pyruvate kinase isoform M2 and peroxiredoxin 6 displayed increased intensities in $TiO_2$ NP-exposed lungs, while three proteins, named heat shock protein, moesin and apolipoprotein A-1 precursor, showed reduced intensities.