MicroRNAs (miRNAs) have been linked to the molecular pathogenesis of many cancers,acting as tumor suppressors or oncogenes.In this study, we found that miR-219-5p was significantly downregulated in 83 HCC tissues and three HCC cell lines, compared to their non-tumor counterparts.MiR-219-5p expression was correlated with tumor size (P =0.027), histological differentiation (P =0.030), and overall survival time (P =0.005)in HCC patients.We also found that miR-219-5p could inhibit cell proliferation in vitro.Further studies identified that miR-219-5p reduced both the mRNA and protein levels of glypican-3 (GPC3).These findings indicate that miR-219-5p exerts tumor-suppressive effects in hepatic carcinogenesis through negative regulation of GPC3 expression.