Drought stress typically causes heavy losses in apple production and uncovering the mechanisms by which apple tolerates drought stress is important in apple breeding. MdSIZ1 is a SUMO (small ubiquitin-like modifier) E3 ligase that promotes SUMO binding to substrate proteins. Here, we demonstrate that MdSIZ1 in apple has a negative relationship with drought tolerance. MdSIZ1 RNAi transgenic apple trees had a higher survival rate after drought stress. During drought stress they had higher leaf water potential, reduced ion leakage, lower H2O2 and malondialdehyde contents, and higher catalase activity. In addition, MdSIZ1 RNAi transgenic plants had a higher net photosynthetic rate during the latter period of drought stress. Finally, the transgenic apple trees also altered expression levels of some microRNAs in response to drought stress. Taken together, these results indicate that apple MdSIZ1 negatively regulates drought stress by enhancing leaf water-holding capacity and antioxidant enzyme activity.