Hepatocellular carcinoma (HCC) is a major health problem worldwide, involving more than 620,000 new cases yearly, with chronic HBV and HCV infection being the most common causes. Because most patients are diagnosed in an advanced state which is usually not amenable to curative therapy, prevention should be the main focus for reducing the HCC incidence and its related morbidity and mortality. Strategies of HCC prevention can focus on each single risk factor, with antiviral therapy against chronic hepatitis B and hepatitis C as well as suppression of the progression of common liver diseases being the most important and effective measures. Bicyclol, a drug that can improve liver function and inhibit HBV replication, may be a useful agent for the chemopreventive of HCC, as indicated by a recent study by Zhu et al. Bicyclol can act on the initiation and promotion stages of hepatocarcinogenesis by preventing malignant transformation of hepatic cells. It may also enhance the liver's capacity of detoxification and inhibit DNA mutations. More clinical studies are needed to further demonstrate the efficacy and molecular mechanisms of this agent on HCC chemoprevention.