It is well established that cellular programs of oncogenic transformation and unresolved wound repair overlap. However, mechanistic parallels between tumour regression upon inhibition of an oncogenic driver and resolution of wounding are poorly understood. To address this, we evaluated spatiotemporally controlled perturbations in mouse models of lung adenocarcinoma driven by oncogenic KRasG12D and conditional Myc cooperation. By RNA sequencing and immune protein profiling of tumours and their attendant microenvironment, we find that loss of Myc activates a local regenerative immune response that mimics tissue repair and specifically eliminates neoplastic cells. We identify interleukin-33 (IL33), an alarmin cytokine, as the key resolution-initiating signal that is produced and transiently secreted by the epithelial tumour cells within hours of Myc deprivation, reversing the immunosuppressive and neoangiogenic tumour microenvironment. IL33 instructs the immune microenvironment to propel tumour cell death, and this depends on eosinophils. Short-term recombinant IL33 treatment of mice harbouring KRas/Myc-driven adenocarcinomas can also trigger this robust repair pathway to unleash durable near-complete tumour regression. Our study reveals how acute oncogene loss can initiate a tissue-intrinsic and injury-associated innate immune programme that promotes neoplastic clearance, and this provides a framework for utilising endogenous tissue repair pathways for targeted cancer therapies.