Augusto Villanueva, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, NY, outlines the need to develop more sensitive methods to detect biomarkers that are indicative of early tumor development in patients predisposed to hepatocellular carcinoma (HCC). Potential liquid biopsy options include the detection of circulating tumor DNA (ctDNA) and respective methylation, mutation, and extracellular vesical analysis, all with increased sensitivity to detect early tumor development for HCC. Detection of specific biomarkers is also clinically relevant in the prediction of tumor response to approved treatments and may aid clinicians in suggesting the best course of treatment for HCC patients with increased efficacy whilst mitigating hepatotoxicity. This interview was conducted at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.