Updated publication reference for PubMed record(s): 29500295. NUAK1 is a member of the AMPK family of kinases involved in regulation of cell adhesion, metabolism and stress responses. Our previous analysis revealed a requirement for NUAK1 to sustain viability when MYC is overexpressed. Human colorectal cancer (CRC) shows near uniform overexpression of MYC, suggesting that this cancer may be particularly amenable to NUAK1 inhibition. This work reveals that elevated NUAK1 expression in human CRC correlates with more aggressive disease, lymph node metastasis and reduced overall survival. Deletion of Nuak1 in murine intestines prevented outgrowth of colonic tumors driven by loss of Apc and KRas mutation, while depletion of Nuak1 in pre-existing tumors drove rapid tumor regression. Mechanistically, we show that NUAK1 promotes anti-oxidant gene expression by facilitating nuclear import of NRF2. Deletion or inhibition of NUAK1 renders cells vulnerable to oxidative stress and provision of exogenous anti-oxidants protects cells in culture and colonic tumors in situ from Nuak1 depletion.