We show that SIRT1 mRNA level, as well as protein level, is overexpressed in HCC samples, and high expression of SIRT1 is remarkedly associated with advanced stage and poor prognosis. Proteomics analysis is performed on SIRT1-overexpressed HepG2 cells and the results reveal that the differently expressed proteins (DEPs) are significantly enriched in autophagy, revealing the pro-effect of SIRT1 on autophagy.