Hydroponic experiments were conducted using cadmium (Cd)-sensitive (cv Guiyan 1) and Cd-tolerant (Yunyan 2) tobacco cultivars to evaluate cultivar differences in response to Cd toxicity in the presence of selenium (Se). The results showed that addition of 3 µM Se in 50 µM Cd solution markedly reduced Cd accumulation in plants, alleviated Cd-induced growth inhibition, and increased nitrogen and chlorophyll contents as well as photosynthetic performance (i.e., net photosynthetic rate, stomatal conductance, and transpiration rate). External Se dramatically depressed Cd-induced O2 (•-) , H2 O2 , and malondialdehyde accumulation, especially in the sensitive cultivar. Selenium significantly elevated Cd-depressed activities of superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, glutathione-peroxidase, and glutathione reductase in the both cultivars after 7-d treatments. Meanwhile, Se counteracted Cd-induced alterations in certain nutrient elements; for example, it significantly increased Zn and Ca concentrations and reduced Mg concentration in both cultivars. Furthermore, Se significantly elevated Cd-depressed H(+) -K(+) -adenosine triphosphatase (ATPase), Na(+) -K(+) -ATPase, and Ca(2+) -Mg(2+) -ATPase activities. The beneficial effect of Se under Cd stress may be related mainly to the increased ATPase activity and reduced Cd uptake and reactive oxygen species accumulation, thus reducing the negative consequences of oxidative stress caused by Cd toxicity.