Homeodomain-leucine zipper （HD-ZIP） transcription factors are widely distributed in plants and play crucial roles in regulating plant growth， development， and responses to abiotic stresses. However， systematic identification and functional characterization of this gene family in foxtail millet （Setaria italica L.） remain unclear. In our previous study， we identified the drought-resistant candidate gene Seita.1G253700.1. With the publicly available genome database of foxtail millet variety Yugu 1 combining with bioinformatics analysis， a systematic identification of the HD-ZIP gene family in foxtail millet is conducted， and its physicochemical properties， phylogenetic relationships， conserved motifs， gene structure， chromosomal location and cis-acting elements are analyzed. The results showed that a total of 29 HD-ZIP family members were identified in foxtail millet， with amino acid lengths ranging from 220 to 422 aa， relative molecular weights ranging from 23.99 kDa to 44.41 kDa， and theoretical isoelectric points from 4.60 to 9.63. All members were predicted to be localized in the nucleus by subcellular localization analysis. According to the phylogenetic tree， the HD-ZIP family members of foxtail millet were distributed in the HD-ZIP Ⅰ and HD-ZIP Ⅱ subfamilies， while no members were found in the HD-ZIP Ⅲ and HD-ZIP Ⅳ subfamilies， and significant differences in motif types and gene structures were observed among members of different subfamilies. The 29 genes were distributed on 7 chromosomes， with chromosome 9 having the largest number of genes， and the number of genes was not proportional to chromosome length. cis-acting element analysis revealed that the HD-ZIP gene family contains multiple abiotic stress-responsive elements， including abscisic acid-responsive elements and drought-inducible MYB binding sites. After transferring the SiHD05 gene into Arabidopsis thaliana， comprehensive analysis of phenotypes and physiological indices showed that overexpression of SiHD05 exacerbated leaf wilting under drought stress and significantly increased the accumulation of superoxide anion and abscisic acid， confirming that this gene negatively regulates drought resistance in Arabidopsis. This study provides a basic data for exploring the mechanism of the homeodomain-leucine zipper SiHD05 in foxtail millet and for research aimed at improving crop stress resistance.