Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. However, the effective pharmacological approaches remain scanty in clinical practice. As a bioactive flavonoid, apigenin (API) is enriched in common fruits and vegetables. Although pharmacological activities of API have been widely investigated, its biological function in HCC remains obscure. In the present study, we found that API strongly suppressed cell growth and induced apoptosis in HCC cells. Using a xenograft mice model, API was demonstrated to inhibit the in vivo tumor growth. It is known that the long non-coding RNA H19, which is frequently elevated in HCC, plays a vital role in mediating tumorigenesis and cancer progression. Our results demonstrated that H19 was down-regulated by API, and thereby induced the inactivation of the canonical Wnt/β-catenin signaling. In conclusion, our results demonstrated that API was able to suppress tumor growth of HCC through H19-mediated Wnt/β-catenin signaling regulatory axis, suggesting that API may be a promising candidate for developing novel therapeutic approaches against liver cancer. Copyright © 2020 Elsevier B.V. All rights reserved.