Amorphous silica has been used in a wide variety of industrial and consumer applications. Nanosized silica is being considered a potentially ideal nanomaterial for biomedical and biotechnological applications. In the present study, hierarchical oxidative stress paradigms of nanoparticle toxicity were assumed to evaluate the toxicity of amorphous silica nanoparticle in human healthy lung cells, L-132. The cells were exposed to varied concentrations viz. 0, 100, 200, 300, 400 and 500 μg/ml of silica nanoparticle for 24 h. Different parameters of cytotoxicity, oxidative stress and pro-inflammatory markers were assessed. Silica nanoparticle exposure showed concentration-dependent decrease in cell viability, increase in reactive oxygen species with depletion of antioxidant enzyme activity, induction of inteleukin-8 and cyclooxygenase-2 expression and subsequent DNA damage in L-132 cells. The results indicated that amorphous silica nanoparticle followed hierarchical oxidative stress model and generated oxidative stress which provoked the pro-inflammatory response and caused necrosis in human lung cells. © 2015, © 2014 Taylor & Francis.