AbstractDrought and cold stresses seriously affect tree growth and fruit yield during apple (Malus domestica) production, with combined stress causing injury such as shoot shriveling. However, the molecular mechanism underlying crosstalk between responses to drought and cold stress remains to be clarified. In this study, we characterized the zinc finger transcription factor ZINC FINGER OF ARABIDOPSIS THALIANA 10 (ZAT10) through comparative analysis of shoot-shriveling tolerance between tolerant and sensitive apple rootstocks. MhZAT10 responded to both drought and cold stresses. Heterologous expression ofMhZAT10in the sensitive rootstock ‘G935' from domesticated apple (Malus domestica) promoted shoot-shriveling tolerance, while silencing ofMhZAT10expression in the tolerant rootstock ‘SH6' ofMalus honanensisreduced stress tolerance. We determined that the apple transcription factor DEHYDRATION RESPONSE ELEMENT-BINDING PROTEIN 2A (DREB2A) is a direct regulator activating the expression ofMhZAT10in response to drought stress. Apple plants overexpressing bothMhDREB2AandMhZAT10genes exhibited enhanced tolerance to drought and cold stress, while plants overexpressingMhDREB2Abut with silenced expression ofMhZAT10showed reduced tolerance, suggesting a critical role of MhDREB2A-MhZAT10 in the crosstalk between drought and cold stress responses. We further identified drought-tolerantMhWRKY31and cold-tolerantMhMYB88andMhMYB124as downstream regulatory target genes of MhZAT10. Our findings reveal a MhDREB2A-MhZAT10 module involved in crosstalk between drought and cold stress responses, which may have applications in apple rootstock breeding programs aimed at developing shoot-shriveling tolerance.