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Oncogenic <i>K-RAS</i> mutations occur in approximately 25% of human lung cancers and are most frequently found in codon 12 (G12C, G12V, and G12D). Mutated K-RAS inhibitors have shown beneficial results in many patients; however, the inhibitors specifically target K-RAS<i>^G12C</i> and acquired resistance is a common occurrence. Therefore, new treatments targeting all kinds of oncogenic <i>K-RAS</i> mutations with a durable response are needed. RUNX3 acts as a pioneer factor of the restriction (R)-point, which is critical for the life and death of cells. <i>RUNX3</i> is inactivated in most <i>K-RAS</i>-activated mouse and human lung cancers. Deletion of mouse lung <i>Runx3</i> induces adenomas (ADs) and facilitates the development of <i>K-Ras</i>-activated adenocarcinomas (ADCs). In this study, conditional restoration of <i>Runx3</i> in an established <i>K-Ras</i>-activated mouse lung cancer model regressed both ADs and ADCs and suppressed cancer recurrence, markedly increasing mouse survival. <i>Runx3</i> restoration suppressed <i>K-Ras</i>-activated lung cancer mainly through Arf-p53 pathway-mediated apoptosis and partly through p53-independent inhibition of proliferation. This study provides in vivo evidence supporting <i>RUNX3</i> as a therapeutic tool for the treatment of <i>K</i>-<i>RAS</i>-activated lung cancers with a durable response.