Significance Pancreatic cancer utilizes autophagy to survive stress and promote therapeutic resistance. However, the metabolic contribution of autophagy in PDAC has not been fully elucidated. We report that SLC7A11 function requires autophagy machinery for proper membrane localization in PDAC, allowing proper cystine transport. Our findings continue to support the use of autophagy inhibition as a therapeutic strategy in pancreatic cancer by demonstrating that this leads to inactivation of SLC7A11 and disruption of cysteine homeostasis.