Using annual Populus pruinosa seedlings as the test material, an experiment of drought and salt stress was carried out by using field salt and water control methods. Growth, physiological, and biochemical indices were used to investigate the growth and adaptation of seedlings under combined salt-drought stress. The results showed that compared to the control group, there were significant differences in the antioxidant enzyme activity, and the MDA and proline contents between Populus pruinosa seedlings under salt, drought and cross-stress. (1) The relative growth of the Populus pruinosa seedlings was significantly inhibited under salt treatments of 8, 11 g/L and 15 g/L, (P < 0.05), while there was no significant difference between drought stress and salt stress. (2) Under salt-drought stress, the activities of antioxidant enzymes SOD, POD, and CAT first increased and then decreased with an increase in the degree of stress, and the difference was significant; the activities of SOD, POD, and CAT were significantly increased under drought stress; (3) Under the conditions of salt, drought, and cross-stress, the MDA content first decreased and then increased, which was in accordance with the trend of increasing the activity of antioxidant enzymes and then decreasing. The proline content increased with significant difference (P < 0.05). Therefore, the activity of antioxidant enzymes has a certain limit on the damage of lipid peroxidation, while the MDA content is negatively correlated with antioxidant enzyme activity, and Populus pruinosa showed some tolerance under salt-drought stress.