Silica nanoparticles (SiO2-NPs) have been demonstrated to alleviate the adverse impacts of salt or low temperature on crop growth, especially for individual stress. The aim of this study was to elucidate the regulatory effect of SiO2-NPs on plant performance under combined salt and low-temperature stress. Therefore, a phytotron experiment was performed to explore the effects of SiO2-NPs application (0, 50, 100, 200 mg L−1) on the plant growth, ionic content, antioxidant activities, photosynthetic parameters, and osmoregulator concentrations of cotton seedlings subjected to the combined stress of salinity (50, 100, and 150 mmol L−1 NaCl) and low temperature (day and night temperatures of 15 and 10 °C). The results indicated that the combinatorial stress strongly decreased the plant height and leaf area of cotton seedlings, and obviously suppressed the aboveground biomass by 10.26 %, 11.42 %, and 15.70 % with the increase in salinity. While SiO2-NPs application significantly increased the plant growth, photosynthetic rate, transpiration rate, stomatal conductance, superoxide dismutase, catalase and glutathione reductase activities, leaf water potential, K+, and proline contents, and reduced the Na+ content and Na+/K+ ratio of cotton seedlings under the combinatorial stress. However, the effects of SiO2-NPs on reduced glutathione, total soluble sugar and protein content, and peroxidase activity did not exhibit a clear pattern. The aboveground biomass of cotton seedlings subjected to the combinatorial stress was closely correlated with the Na+/K+ ratio, Na+ content, K+ content, proline content, SOD activity, and CAT activity, indicating that SiO2-NPs could alleviate the suppression of combinatorial stress on cotton seedling growth by decreasing the Na+/K+ ratio and increasing the antioxidant capacity.