MicroRNAs (miRNA) are relevant regulators of the tumorigenesis of various cancers, such as hepatocellular carcinoma (HCC). Recent studies have suggested that miR-542-3p is a tumor suppressor gene in numerous cancers. However, the role of miR-542-3p in HCC remains unclear. This study showed that miR-542-3p was downregulated in HCC tissues and cell lines. MTT, colony formation, and cell cycle assays revealed that miR-542-3p overexpression inhibited HCC cell growth, whereas miR-542-3p suppression promoted cell growth. Frizzled7 (FZD7), the most important Wnt receptor involved in cancer development and progression, was identified as a functional target of miR-542-3p through dual-luciferase reporter assay, RT-qPCR, and Western blot. The mRNA expression of FZD7 was inversely correlated with miR-542-3p expression in HCC tissues. miR-542-3p overexpression could significantly decrease the activation of Wnt signaling pathway in HCC cells. FZD7 overexpression could significantly reverse the inhibitory effect of miR-542-3p on HCC cell growth and Wnt signaling pathway. Taken together, our study suggests that miR-542-3p inhibits HCC cell growth by targeting FZD7 and inhibiting Wnt signaling pathway. The decreased miR-542-3p expression may also contribute to the progression of HCC and may represent a novel molecular therapeutic target for HCC. (C) 2016 Elsevier Inc. All rights reserved.