Our results showed that IGF2-AS expression was significantly down-regulated in HCC cells and tissues; lower IGF2-AS expression was significantly associated with poor prognosis of HCC patients; IGF2-AS over-expression inhibited the viability, colony formation, invasion, and migration, while promoted apoptosis in vitro, and inhibited HCC xenograft growth in vivo; IGF2-AS sponged microRNA-520h (miR-520h) to up-regulate IGF2-AS expression, and miR-520h over-expression or cyclin-dependent kinase inhibitor 1A (CDKN1A) silencing reversed IGF2-AS reduced aggressive behaviors of HCC cells. This evidence concerns the gene IGF2 and hepatocellular carcinoma.