Our current study strengthened the connection that AEG-1, a key driver of HCC, is palmitoylated, which negatively regulates its protein stability via proteasome mediated degradation pathway; inhibiting AEG-1 palmitoylation enhances its binding to SND1 and thus the RISC activity, the latter may downregulate the mRNA level of several tumor suppressors as PTEN/TGFB2 and therefore promotes HCC progression. This evidence concerns the gene MTDH and hepatocellular carcinoma.