Autophagy is a cellular process that degrades cytoplasmic proteins and organelles and has been implicated in tumor suppression. This study shows that mice with systemic mosaic deletion of Atg5 and liver-specific Atg7 knockout develop benign liver adenomas. These tumors originate from autophagy-deficient hepatocytes and exhibit mitochondrial swelling, p62 accumulation, and oxidative stress. The size of Atg7-deficient liver tumors is reduced by simultaneous deletion of p62, suggesting that autophagy is important for suppressing spontaneous tumorigenesis, particularly in the liver. The accumulation of p62 contributes to tumor progression. The study also indicates that autophagy may be required for progression beyond the benign state. The results suggest that autophagy plays a critical role in preventing liver tumor development through a cell-intrinsic mechanism. The findings highlight the importance of autophagy in maintaining liver homeostasis and preventing tumorigenesis. The study provides new insights into the role of autophagy in tumor suppression and the mechanisms underlying liver tumor development.Autophagy is a cellular process that degrades cytoplasmic proteins and organelles and has been implicated in tumor suppression. This study shows that mice with systemic mosaic deletion of Atg5 and liver-specific Atg7 knockout develop benign liver adenomas. These tumors originate from autophagy-deficient hepatocytes and exhibit mitochondrial swelling, p62 accumulation, and oxidative stress. The size of Atg7-deficient liver tumors is reduced by simultaneous deletion of p62, suggesting that autophagy is important for suppressing spontaneous tumorigenesis, particularly in the liver. The accumulation of p62 contributes to tumor progression. The study also indicates that autophagy may be required for progression beyond the benign state. The results suggest that autophagy plays a critical role in preventing liver tumor development through a cell-intrinsic mechanism. The findings highlight the importance of autophagy in maintaining liver homeostasis and preventing tumorigenesis. The study provides new insights into the role of autophagy in tumor suppression and the mechanisms underlying liver tumor development.