Further investigation showed that NOD2 exerted its anti-tumor effect through activating adenosine 5′-monophosphate (AMP) -activated protein kinase (AMPK) signaling pathway, and NOD2 significantly enhanced the sensitivity of HCC cells to sorafenib, lenvatinib and 5-FU treatment through activating AMPK pathway induced apoptosis. This evidence concerns the gene NOD2 and neoplasm.