A key regulator of sorafenib sensitivity, CFL1, was identified, primarily in relation to the remodeling of the cytoskeleton and cell motility. High CFL1 expression enhances serine synthesis and metabolism, as well as the scavenging of sorafenib-induced excess reactive oxygen species (ROS). Consequently, this leads to a diminished sensitivity of hepatocellular carcinoma (HCC) cells to sorafenib. The gene discussed is CFL1; the disease is hepatocellular carcinoma.