Agrimol B inhibits hepatocellular carcinoma growth by initiating autophagy and blocking autophagosome-lysosome fusion, driven by caspase 3-mediated degradation of NDUFS1, which leads to mitochondrial reactive oxygen species accumulation and autophagy arrest, enhancing the efficacy of sorafenib in treating HCC. Here, NDUFS1 is linked to hepatocellular carcinoma.