<p>The purinergic ligand-gated ion channel 7 receptor (P2X7R) is a non-selective ion channel activated by extracellular adenosine triphosphate. It promotes intracellular signal transduction by inducing Na⁺ and Ca²⁺ influx and K⁺ efflux. Moreover, this receptor is involved in the regulation of the inflammatory response, oxidative stress, cell death, and immune response. P2X7R is associated with the onset and progression of various chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and pulmonary tuberculosis. In this review, we comprehensively summarize the structure and functions of P2X7R as well as its roles and potential molecular mechanisms in chronic respiratory diseases. Additionally, we explored the application of P2X7R antagonists in clinical practice. In summary, targeting P2X7R may be a new strategy for treating chronic respiratory diseases, but we should still pay attention to its dual roles, especially in lung cancer.</p>