This study reveals that autophagy plays a crucial role in regulating cilia length and mucociliary clearance disruption in chronic obstructive pulmonary disease (COPD) due to cigarette smoke exposure, identifying HDAC6 as a key regulator of this autophagy-mediated process, and suggesting that targeting this pathway may offer therapeutic benefits for COPD. Here, HDAC6 is linked to chronic obstructive pulmonary disease.