Patients with chronic obstructive pulmonary disease (COPD) are more susceptible to influenza A virus (IAV) with more severe symptoms, yet the underlying molecular mechanisms of the hypersusceptibility of airway inflammatory response remain unclear. The primary human bronchial epithelial cells (pHBECs) were isolated from normal and COPD bronchial tissues (NHBE and DHBE) and cultured with/without IAV infection . DHBE cells were exposed to IAV for 24 h after knockdown of lncRNA TUG1 with short hairpin RNA (shRNA). Gain-of-function assays were performed with the miR-145-5p inhibitor and NF-κBp65 transfection. The expressions of lncRNA TUG1, miR-145-5p, phospho-NF-κBp65, NF-κBp65, TNF-α, and (Interleukin) IL-1β were examined with qRT-PCR, Western blotting, and ELISA. The interactions of lncRNA TUG1, miR-145-5p, and NF-κB were verified with luciferase reporter assay. The expressions of lncRNA TUG1, phospho-NF-κBp65, TNF-α, and IL-1β were increased significantly in pHBECs after being infected with IAV for 24 h (all 0.05). The detailed time analysis revealed that the NF-κBp65 in DHBE was activated earlier than that in NHBE by Western blotting and immunofluorescence. Knockdown of lncRNA TUG1 and miR-145-5p mimic attenuated the expressions of NF-κBp65, TNF-α, and IL-1β significantly. The miR-145-5p inhibitor and NF-κBp65 transfection reversed the attenuated expressions of NF-κBp65, TNF-α, and IL-1β. The IAV causes the hypersusceptibility of airway inflammatory response, which may be closely associated with more severe symptoms in AECOPD patients. The lncRNA TUG1 inhibitor may be a promising therapeutic strategy for AECOPD caused by IAV.