Hepatocellular carcinoma (HCC) is a major cause of death among patients with advanced chronic liver disease, and established therapies for chemoprevention of HCC are lacking. Aspirin and statins have been identified as promising potential agents for HCC chemoprevention in patients with chronic liver disease, through diverse anti-inflammatory and anti-neoplastic effects. Findings from in vitro studies and animal models strongly indicate protective effects of aspirin and statins against both the development and progression of HCC. Results from some observational clinical studies further support these associations. However, robust data from randomized clinical trials (RCTs) is still lacking; thus, further research is still needed before either aspirin or statins can be recommended as a chemopreventive standard in patients with chronic liver disease.