Hepatocellular carcinoma is a major public health problem, ranking as the third cause of cancer‐related deaths globally. There has been a net increase of 62% in HCC‐related annual death rates during the past 20 years. Image‐guided tumor ablation is now a conventional treatment option for patients with early‐ stage HCC. The main cause of local treatment failure is high incidence of HCC recurrence. Reports demonstrate recurrence rates after treatment for HCC of approximately 70%. Therapeutic strategies to address these high recurrence rates are sorely needed. Our preliminary works demonstrate that cells that survive initial ablation insult in the outer rim of the ablation zone overexpress FGF19. We hypothesize that ablation therapy creates an FGF19‐rich microenvironment, due to up regulation in wound‐healing and proliferation stimulatory signaling. The goal of the current proposal is to understand the association between alterations on FGF19/FGFR4 pathway and the development of HCC recurrence, after tumor ablation.