Abstract Background The AP2/ERF (APETALA 2/ethylene-responsive element binding factors) is a class of superfamily of plant-specific transcription factor that play an important regulatory role in many physiological and biochemical processes in plants. Results In this study, overexpression of the StERF79 gene increased drought tolerance in potato plants, whereas StERF79 RNA interference expression (RNAi) lines decreased drought tolerance in potato plants. In addition, the superoxide dismutase (SOD), peroxide dismutase (POD), and catalase (CAT) activities, as well as proline (Pro) content of StERF79 transgenic lines, showed significantly higher results than those of the wild type (WT) potato plants under natural drought stress conditions, while the malondialdehyde (MDA) content was lower. The StERF79 transcription factor can respond to drought stress by interacting with a DRE cis-acting element in the promoter region of the downstream target gene (StDHN-2), and activating its expression, the result was validated by using yeast one hybrid (Y1H), Dual-Luciferase and β-glucuronidase (GUS) staining assays both in vivo and in vitro. The StDHN-2 gene is a member of the dehydrin (DHN) subfamily of the potato plant late embryonic developmentally abundant (LEA) protein family. LEA, hydrophilic proteins found in plants, serve as cellular dewatering protectants to prevent desiccation during various stresses. Conclusion The results could provide novel knowledge into the functional analysis of the StERF79 gene in positive regulation of the StDHN-2 gene to drought response and its possible mechanisms in potato plants. Clinical trial number Not applicable.