Autophagy promotes ferroptosis by degrading ferritin. This study shows that autophagy contributes to ferroptosis by degrading ferritin in fibroblasts and cancer cells. Knockout or knockdown of Atg5 and Atg7 limited erastin-induced ferroptosis, as well as decreased intracellular ferrous iron levels and lipid peroxidation. NCOA4 is a selective cargo receptor for the autophagic turnover of ferritin (ferritinophagy) in ferroptosis. Genetic inhibition of NCOA4 inhibited ferritin degradation and suppressed ferroptosis, while overexpression of NCOA4 increased ferritin degradation and promoted ferroptosis. These findings suggest that autophagy and regulated cell death interact in a complex manner. Autophagy is an evolutionarily conserved degradation pathway that maintains homeostasis. Ferroptosis is a novel form of regulated cell death characterized by the production of reactive oxygen species from accumulated iron and lipid peroxidation. The study shows that autophagy-related genes play a central role in the mediation of autophagy. Atg5 and Atg7 are critical for the formation of the autophagosome. The study also shows that NCOA4 is involved in the degradation of ferritin, which is a major intracellular iron storage protein. The findings suggest that autophagy contributes to ferroptosis by degrading ferritin. This study provides important evidence that activation of the autophagy pathway promotes ferroptosis by degradation of ferritin in fibroblasts and cancer cells. The study also shows that impaired ferroptosis has been identified in various human diseases such as neurodegenerative diseases, ischemia/reperfusion injury, infectious diseases, and cancers. Further functional characterization of the ATG5-ATG7-NCOA4 autophagic pathway in ferroptosis may provide insight into the treatment of diseases of iron metabolism.Autophagy promotes ferroptosis by degrading ferritin. This study shows that autophagy contributes to ferroptosis by degrading ferritin in fibroblasts and cancer cells. Knockout or knockdown of Atg5 and Atg7 limited erastin-induced ferroptosis, as well as decreased intracellular ferrous iron levels and lipid peroxidation. NCOA4 is a selective cargo receptor for the autophagic turnover of ferritin (ferritinophagy) in ferroptosis. Genetic inhibition of NCOA4 inhibited ferritin degradation and suppressed ferroptosis, while overexpression of NCOA4 increased ferritin degradation and promoted ferroptosis. These findings suggest that autophagy and regulated cell death interact in a complex manner. Autophagy is an evolutionarily conserved degradation pathway that maintains homeostasis. Ferroptosis is a novel form of regulated cell death characterized by the production of reactive oxygen species from accumulated iron and lipid peroxidation. The study shows that autophagy-related genes play a central role in the mediation of autophagy. Atg5 and Atg7 are critical for the formation of the autophagosome. The study also shows that NCOA4 is involved in the degradation of ferritin, which is a major intracellular iron storage protein. The findings suggest that autophagy contributes to ferroptosis by degrading ferritin. This study provides important evidence that activation of the autophagy pathway promotes ferroptosis by degradation of ferritin in fibroblasts and cancer cells. The study also shows that impaired ferroptosis has been identified in various human diseases such as neurodegenerative diseases, ischemia/reperfusion injury, infectious diseases, and cancers. Further functional characterization of the ATG5-ATG7-NCOA4 autophagic pathway in ferroptosis may provide insight into the treatment of diseases of iron metabolism.