MicroRNAs (miRNAs) are involved in regulating various physiologic and pathologic processes of different human diseases including hepatocellular carcinoma (HCC). Our research aimed to investigate the role of miR-497 in migration, invasive ability of HepG2-GS cells and the regulating mechanism. In this study, Rictor was identified as a target gene of miR-497 by informatic software, including Microcosm Targets, miRanda, and TargetScan. MiR-497 or Rictor were silenced or overexpressed in HepG2-GS cells through transfection. The functional assay results showed that Rictor knockdown inhibited cancer cell proliferation, migration and invasion. Overexpression of Rictor inversed the effects of miR-497 on cancer cells growth inhibition. miR-497 regulated protein kinase B, PKB (Akt) signaling pathway by targeting Rictor. MiR-497 increased chemo-sensitivity of HepG2-GS through regulation of Rictor. In conclusion, our research demonstrated that miR-497 inhibits the proliferation, invasion, metastasis, and chemotherapy resistance of hepatoma cells by targeting of Rictor/Akt signal pathway, and miR-497. Thus, Rictor has the potential to be a explored as a biomarker or therapeutic target for diagnosis and treatment of HCC.