The cytotoxicity of silica nanoparticles (NPs) was investigated in the human lung cell line, A549. Silica NPs of different sizes (DLS size; 16-42 nm) were used to determine appropriate dose metrics whereas the effect of the NP corona was tested by coating the NPs with bovine serum albumin (BSA). The NPs were characterized by TEM and DLS as monodisperse and non-aggregated in solution and the NP suspensions were free of metal and endotoxin impurities as tested by ICP-MS and the LAL test. Cellular uptake and binding of the silica NPs was indirectly assessed by flow cytometry side scatter and SEM. Cytotoxicity was measured by the MTT and LDH assays as markers of mitochondrial damage and membrane leakage, respectively, whereas the production of reactive oxygen species (ROS) was measured by the fluorescent probe H2DCFH-DA. The inflammatory potential of the NPs was estimated by cellular secretion of IL-8 upon silica NP exposure. The silica NP surface area was found to be the best dose metric for predicting cytotoxicity and IL-8 release. Generally, the NPs were only cytotoxic at high concentrations and BSA-coating of the NPs significantly decreased the cytotoxicity and cellular IL-8 secretion. All the NPs were found to cause increased cellular ROS production which could not be reduced by antioxidant treatment. In conclusion, our data suggest that surface area is an appropriate dose metric to predict cytotoxicity and inflammation induced by silica nanoparticles. Furthermore, the reduced toxicity of BSA-coated silica NPs indicates that exposure conditions should be carefully controlled when testing the effects of NPs.