In prostate, HCC, neuroblastoma, and lung cancer cells, NEDD4-1 is highly expressed and favors tumorigenesis and positively regulates autophagy initiation via the inhibition of mTORC1, the phagophore nucleation via stabilization of VPS34-Beclin-1 complex, the phagophore elongation via interaction with LC3-I, as well as cargo selection via stabilization of the autophagy receptor SQSTM1. Here, NEDD4 is linked to hepatocellular carcinoma.