Radiation therapy triggers senescence in thyroid cancer cells, but these supposedly dormant cells develop a cunning survival strategy. When radiation disrupts their cellular recycling system (autophagy), it causes SQSTM1/p62 protein accumulation, which activates the Nrf2 antioxidant pathway. This creates a protective shield against oxidative stress that would normally kill senescent cells. The research reveals that TFEB, the master regulator of lysosomal biogenesis, fails to properly relocate to the nucleus in these senescent cells, creating the autophagic dysfunction that paradoxically enhances their survival. This finding illuminates why the "one-two punch" therapeutic approach—using radiation followed by senolytic drugs to eliminate lingering senescent cells—often fails in aggressive thyroid cancers. The Nrf2-mediated resistance mechanism helps explain why dedifferentiated thyroid tumors remain so therapeutically challenging. Understanding this survival pathway opens new avenues for combination therapies that could simultaneously block Nrf2 signaling while targeting senescent cells, potentially preventing cancer recurrence and metastasis that senescent cells are known to drive through inflammatory signaling.