Purpose: To explore the effects of circular ribonucleic acid (circRNA)-E3 ubiquitin protein ligase (ITCH) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells and its possible molecular mechanism. Methods: To study the role of circRNA-ITCH in the occurrence and development of HCC. The relative expression level of circRNA-ITCH was detected via quantitative polymerase chain reaction (qPCR) in four kinds of HCC Huh-7, U251, HB611 and SMMC-7721 cell lines, and human normal liver L-02 cell line. Moreover, the effect of overexpression of circRNA-ITCH on the TCF luciferase activity was detected using beta-catenin/TCF-responsive luciferase reporter assay. Finally, the influences of overexpression of circRNA-ITCH on the protein levels of beta-catenin and Wnt3a and the mRNA levels of c-myc and cyclinD1 were determined using Western blotting and qPCR, respectively. Results: Compared with that in human normal liver L-02 cell line, the expression of circRNA-ITCH was significantly down-regulated in HCC Huh-7, U251, HB6I1 and SMMC-7721 cell lines (p <0.05). According to the results of CCK-8 assay, colony formation assay and flow cytometry, the overexpression of circRNA-ITCH could obviously inhibit cell proliferation, suppress colony formation ability and induce apoptosis (p<0.05). The results of dual-luciferase reporter assay revealed that there was a significant interaction between circRNA-ITCH and miR-7 or miR-214 (p <0.05). CircRNA-ITCH was involved in the regulating of Wnt/beta-catenin signal transduction pathway and inhibited the expressions of c-myc and cyclinD1. Conclusions: CircRNA-ITCH affects the proliferation and apoptosis of HCC cells through inhibiting the Wnt/beta-catenin signal transduction pathway, thereby exerting a carcinogenic effect in the occurrence and development of HCC. The research results provide a new therapeutic target for HCC.