Here, we identified HDAC6 as the predominant α-tubulin deacetylase in HCC cells: HDAC6 inhibition or depletion enhanced microtubule acetylation and promoted migration and invasion in HCC cells, whereas the protein level and distribution of acetylated microtubules were not obviously affected by sirtuin 2 suppression. This evidence concerns the gene SIRT2 and hepatocellular carcinoma.