This study aims to explore how microRNA-145 (miR-145) affects airway remodeling and cytokine expression by targeting epidermal growth factor receptor (EGFR) to regulate mucin 5AC (MUC5AC).Mice alveolar epithelial cells (AECs) were divided into a control, blank, miR-145 mimics, mimic control, miR-145 inhibitors, inhibitor control, si-EGFR and miR-145 inhibitors + si-EGFR group. Asthma mice models with airway remodeling were induced with an Ovalbumin (OVA) solution and randomly divided into a normal, asthma, asthma + miR-145 mimics, asthma + miR-145 mimic control, asthma + si-EGFR or asthma + si-EGFR NC group. Airway remodeling degree and histomorphology was measured using hematoxylin-eosin (HE), Masson and periodic acid-Schiff (PAS) staining. Flow cytometry was used to detect Th2 and Th17 cells in peripheral blood, ELISA was used to measure inflammatory factors. qRT-PCR and western blotting was adapted to detect the expressions of EGFR and the relevant cytokines that are regulated by miR-145.The control, miR-145 mimics and si-EGFR groups showed a higher expression of miR-145 and a lower expression of EGFR and cytokines than the blank, mimic control, inhibitor control and miR-145 inhibitor + si-EGFR groups. Mice in the asthma + miR-145 mimics and asthma + si-EGFR groups showed lower WAt/Pbm, WAi/Pbm and WAm/Pbm, less inflammatory cells, less airway modeling and alleviated goblet cell hyperplasia and mucus obstruction than the asthma group. Furthermore, the expressions of EGFR and cytokines of transfected cells and lung tissues were negatively related to those of miR-145. MiR-145 can down-regulate MUC5AC by negatively targeting EGFR and thereby relieving airway remodeling.