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‐SiO₂) 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‐SiO₂ improved seed germination and growth characteristics by reducing malondialdehyde and hydrogen peroxide levels as well as electrolyte leakage. In addition, application of nano‐SiO₂ 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‐SiO₂ 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‐SiO₂ 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