Abstract Research into nanotechnology, an emerging science, has advanced in almost all fields of technology. The aim of the present study was to evaluate the role of nano‐silicon dioxide (nano‐SiO 2 ) in plant resistance to salt stress through improvement of the antioxidant system of squash ( Cucurbita pepo L. cv. white bush marrow). Seeds treated with NaCl showed reduced germination percentage, vigor, length, and fresh and dry weights of the roots and shoots. However, nano‐SiO 2 improved seed germination and growth characteristics by reducing malondialdehyde and hydrogen peroxide levels as well as electrolyte leakage. In addition, application of nano‐SiO 2 reduced chlorophyll degradation and enhanced the net photosynthetic rate ( P n ), stomatal conductance ( g s ), transpiration rate, and water use efficiency. The increase in plant germination and growth characteristics through application of nano‐SiO 2 might reflect a reduction in oxidative damage as a result of the expression of antioxidant enzymes, such as catalase, peroxidase, superoxide dismutase, glutathione reductase, and ascorbate peroxidase. These results indicate that nano‐SiO 2 may improve defense mechanisms of plants against salt stress toxicity by augmenting the P n , g s , transpiration rate, water use efficiency, total chlorophyll, proline, and carbonic anhydrase activity in the leaves of plants. Environ Toxicol Chem 2014;33:2429–2437 . © 2014 SETAC