Significance This study demonstrates that damage to lung epithelial architecture induces aberrant cellular signals that promote the development of precancerous airway lesions. These signals are mediated by the uncontrolled activation of the transcriptional effectors YAP and TAZ, which drive the expression of the growth factor NRG1 and the consequent activation of the ERBB receptors. Genetic deletion of YAP/TAZ or pharmacological inhibition of ERBB receptors prevents and treats precancer airway lesion development following epithelial damage, offering important knowledge that may guide therapeutic strategies for intercepting the development of squamous lung cancers.