Currently, therapeutic targeting of CSCs to improve treatment outcomes has been proposed but remains highly challenging.[3, 6] Having revealed LIF as a potent CSCs driver, we have found that selective disruption of LIF‐SE or/and LIF/LIFR‐STAT3 potently impaired tumor growth at least in part by reducing CSCs numbers and their tumorigenic activities in multiple preclinical models. Here, LIF is linked to neoplasm.