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In this study, through analysis of the genome of Eleutherococcus senticosus (ES). 228 AP2/ERF genes were identified and classified into 5 groups AP2 (47 genes), ERF (108 genes), RAV (6 genes), DREB (64 genes), and soloist (3 genes). According to the AP2/ERF classification of Arabidopsis thaliana, the ES AP2/ERF proteins were subdivided into 15 groups. The gene structure and motifs of each group of AP2/ERF in ES were highly similar, which confirmed the conservation of AP2/ERF genes. The ES AP2/ERF genes were unevenly distributed on chromosomes, and a total of four pairs of tandem repeats, and 84 co-linear gene pairs were found, so the AP2/ERF genes expanded in a fragment replication manner, and dominated by pure selection during evolution. By analyzing the transcriptome data of ES under different drought stress conditions, 87 AP2/ERF genes with differential expression were obtained, of which 10 genes with highly significant differences were further analyzed and screened for qRT-PCR validation. To the best of our knowledge, this is the first report on the AP2/ERF gene of Eleutherococcus senticosus, and the bioinformatics analysis and experimental validation provided valuable information about them, which is of great significance for further research on the molecular mechanisms of ES in response to drought stress. [ABSTRACT FROM AUTHOR]