Taken together, our results show that the susceptible crosstalk between apoptosis and autophagy in response to a combination of the epigenetic modulators vorinostat and decitabine in HCC could be attributed to several autophagic and apoptotic proteins including LC3 II, Beclin-1, Bcl-2, ATG5, and caspaseBeclin-3. This evidence concerns the gene ATG5 and hepatocellular carcinoma.