AGO2 (Argonaute RISC Catalytic Component 2) plays an important role in small RNA-guided gene silencing processes. It has been implied in tumorigenesis of different types of tumors. In this study, we found that AGO2 expression was remarkably increased in human hepatocellular carcinoma (HCC) tissues when compared with adjacent noncancerous tissues. High expression of AGO2 was associated with poor prognosis in HCC patients. The CRISPR/Cas9-mediated knockout of AGO2 in SMMC-7721 cells inhibited cell proliferation and induced significant G1 phase arrest of cell cycle. Inhibition of cell migration was also observed in SMMC-7721 AGO2(-/-) cells. In vivo experiments showed that tumors grew slower in nude mice transplanted with AGO2(-/-) cells than in SMMC-7721 cell-derived xenograft mice. Microarray analysis and western blot analysis revealed that AGO2 depletion decreased expression of Survivin, Vimentin, and Snail. Overexpression of AGO2 in SMMC-7721 and Huh-7 cells could reverse the knockout-induced inhibition effects on either cell behaviors or expression of Survivin, Vimentin, and Snail Therefore, our data demonstrated that AGO2 might facilitate HCC tumorigenesis and metastasis through modulating expression of Survivin, Vimentin, and Snail.