Altogether, these data collectively verified that NOD2 exerted its anti-tumor effect by activating AMPK pathway and inducing autophagy-mediated apoptotic cell death of HCC cells, which finally reversed the malignant behaviors of HCC cells and enhanced the chemosensitivity of HCC cells to sorafenib, lenvatinib and 5-FU treatment (Fig. 6e). The gene discussed is NOD2; the disease is hepatocellular carcinoma.