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It is well documented that the homeodomain-leucine zipper (HD-Zip) transcription factors play diverse roles during plant growth and development. The Class I HD-Zip genes are shown to be involved in the regulation of abiotic stress responses and tolerance. Herein, a novel Class I HD-Zip gene, EsHD1, was isolated from Eutrema salsugineum, and an investigation was performed of its physiological functions in response to drought stress. The analyses of gene expression profiles revealed that the EsHD1 transcripts quickly accumulated upon exposure to various abiotic stress conditions or abscisic acid treatments. Furthermore, the overexpression of EsHD1 in tobacco plants conferred improved tolerance to drought stress. The EsHD1-overexpressing lines had lower levels of reactive oxygen species (ROS), ion leakage, and malondialdehyde, but they manifested higher activities of antioxidant enzymes and the transcription of pathogenic-related genes as compared to wild-type plants under drought stress conditions. Therefore, our findings demonstrated that EsHD1 positively regulated plant drought tolerance via alleviation of ROS-mediated membrane damage.