Liver cancer is a heterogeneous aggressive tumor and has an extremely high death rate worldwide [1]. An estimated 1.3 million people will die from liver cancer by 2040 (an increase of 56.4 % from 2020) [2]. Hepatocellular carcinoma (HCC) accounts for 90 % of all liver cancers. Some of the risk factors for HCC include hepatitis B and hepatitis C viruses, alcoholic liver disease, and non-alcoholic fatty liver disease [3]. Early stages of HCC can be treated with locoregional treatments, such as surgical resection, liver transplantation, or Radio-Frequency Ablation. However, most HCC cases are diagnosed at advanced stages, making these treatments ineffective [4]. Metastasis is one of the major obstacles to the cure of HCC [5]. Currently, tyrosine kinase inhibitors (TKIs) are primarily used for treating advanced HCC, however, which benefit only 30 % of patients and cause drug resistance within 6 months [4,6]. Therefore, developing new and more effective agents is needed to improve the treatment and outcome of HCC.

Recently, natural products have been becoming candidates for clinical anticancer drugs due to their various bioactivities and low toxicity [7]. Licorice (Glycyrrhiza uralensis Fisch) is a traditional herbal medicine and has multiple pharmacological effects in various diseases [8]. Its extracts or isolated compounds have been shown as potential anticancer or chemopreventive agents [9]. Licoricidin is a prenylated isoflavone isolated from licorice and shows potential beneficial effects in human diseases [10]. In recent years, the outstanding performance of licoricidin in cancer treatment has received extensive attention. For example, licoricidin exhibits various biological activities against osteosarcoma [11], gastric cancer [12], cervical cancer [13], and prostate cancer [14]. However, the anticancer activity of licoricidin in HCC and the related mechanism remain unknown.

This study comprehensively investigated the anti-HCC potential of licoricidin using cell models and animal models. We hypothesized that licoricidin could inhibit HCC through preventing cancer growth and metastasis. This study suggests the potential of licoricidin as a promising drug candidate for the treatment of HCC and may provide insights that could aid the development of novel therapeutic agents to improve clinical outcomes for patients with liver cancer.