Asthma, a prevalent allergic disease affecting approximately 300 million individuals globally, remains a significant public health challenge. Mesenchymal stromal cells (MSCs) and hepatocyte growth factor (HGF), both recognized for their immunomodulatory properties, hold therapeutic potential for asthma. However, their precise mechanisms remain underexplored. The current study aimed to engineer human HGF overexpressing human dental pulp stromal cells (HGF-DPSCs) and evaluate their efficacy in asthma management while elucidating underlying mechanisms. The results showed that the constructed HGF-DPSCs overexpressed HGF both in vitro and in vivo. Also, compared with DPSCs, they demonstrated a more pronounced distribution within lung tissue. In house dust mite (HDM)-induced asthma, HGF-DPSCs showed a more significant inhibitory effect on airway hyperresponsiveness (AHR), inflammatory infiltration, and CD4