Activating mutations in the RAS oncogene are common in cancer but are difficult to therapeutically target.RAS activation promotes autophagy, a highly regulated catabolic process that metabolically buffers cells in response to diverse stresses.Here we report that Casein Kinase 1 alpha (CK1c), a ubiquitously expressed serine/threonine kinase, is a key negative regulator of oncogenic RAS-induced autophagy.Depletion or pharmacologic inhibition of CK1α enhances autophagic flux in oncogenic RAS-driven human fibroblasts and multiple cancer cell lines.FOXO3A, a master longevity mediator that transcriptionally regulates diverse autophagy genes, is a critical target of CK1α.Oncogenic RAS increases CK1α protein abundance via PI3K-AKT-mTOR activation.CK1α phosphorylation of nuclear FOXO3A then inhibits the transactivation of genes critical for RAS-induced autophagy.Importantly, pharmacologic CK1α inactivation synergizes with lysosomotropic agents to reverse the growth of oncogenic RAS-driven cancer cells and xenografts.Targeting CK1c-regulated autophagy offers a new therapeutic opportunity to treat oncogenic Ras-driven cancers.