Styrene is a volatile organic compound (VOC) that is widely used as an intermediate in many industrial settings. There are known adverse health effects at environmentally significant concentrations, but little is known about the molecular effect of exposure to styrene at subacute toxic concentrations. We exposed human lung epithelial cells, at a wide range of concentrations (1 mg/m3-10 g/m3), to styrene and analyzed the effects on the proteome level by 2-DE, where 1,380 proteins spots were detected and 266 were identified unambiguously by mass spectrometry. A set of 16 protein spots was found to be significantly altered due to exposure to styrene at environmentally significant concentrations of 1-10 mg/m3 (0.2 – 2.3 ppm). Among these, superoxide dismutase [Cu-Zn] as well as biliverdin reductase A could be correlated with the molecular pathway of oxidative stress, while eukaryotic translation initiation factor 5A-1, ezrin, lamin B2 and voltage dependent anion channel 2 have been reported to be involved in apoptosis. Treatment with styrene also caused formation of styrene oxide-protein adducts, specifically for thioredoxin reductase 1. These results underline the relevance of oxidative stress as a primary molecular response mechanism of lung epithelial cells to styrene exposure at indoor-relevant concentrations.