Recently, nanomaterials have become an integral part of our daily lives. However, there is increasing concern about the potential risk to human health. Here, we attempted to identify biomarkers for predicting the exposure and toxicity of nanomaterials by using a proteomics based approach. We evaluated the changes of protein expression in plasma after treatment with silica nanoparticles. Our analyses identified haptoglobin, one of the acute phase proteins, as a candidate biomarker. The results of ELISA showed that the level of haptoglobin was significantly elevated in plasma of mice exposed to silica nanoparticles with a diameter of 70 nm (nSP70) compared to normal mice and those exposed to silica particles with a diameter of 1000 nm. Furthermore, the other acute phase proteins, C-reactive protein (CRP) and serum amyloid A (SAA) were also elevated in plasma of nSP70 treated mice. In addition, the level of these acute phase proteins was elevated in the plasma of mice after intranasal treatment with nSP30. Our results suggest that haptoglobin, CRP and SAA are highly sensitive biomarkers for assessing the risk of exposure to silica nanoparticles. We believe this study will contribute to the development of global risk assessment techniques for nanomaterials.