This study was designed to determine whether nano-sized ZnO has the potential to causeacute cutaneous irritation using cultured HaCaT keratinocytes and a human skin equivalent asin vitro models, compared to non-nanomaterials. Commercial nano ZnO with different sizes (50 nmand 100 nm) was characterized by dynamic light scattering (DLS) and microscopy (SEM) in differentmedia. Nano ZnO reduced the cell viability of HaCaT in a dose-dependent and time-dependentmanner, in a similar way to macro ZnO. However, the 3D-epidermis model revealed no irritation at1 mg/mL after 24 h of exposure. In conclusion, nano-sized ZnO does not irritate skin, in a similarmanner to non-nano ZnO.