Adult lung is a highly quiescent organ,with extremely low cell turnover frequency.However,emerging evidences support the occurrence of repair and regeneration in pulmonary epithelia in response to various injuries.Lung regeneration mainly depends on the proliferation of regionally distributed pulmonary stem cells that re-enter the cell cycle.Genetic lineage-tracing approaches help to track the lung epithelial dif-ferentiation and/or de-differentiation path,and single-cell transcriptomic technique reveals the essential molecular signaling involved in lung regeneration.Dysregulation of the molecular signaling that balances quiescence and self-renewal leads to the transformation of lung stem cells,and thus promotes lung cancer development.Interestingly,different subtypes of lung cancer share common cells of origin and the path-ological transition among various subtypes is responsible for drug resistance in the clinic.In this review,we summarize the recent understanding of lung stem cells in regeneration and tumorigenesis as well as related molecular mechanisms,with the hope to provide helpful insights for clinical treatments of respiratory diseases.