The aims of the present study were three-fold: first, to characterize the molecular prognostic subtype of two phenotypically distinct HCC cell lines used for testing thermal ablation hypotheses and determine their thermal sensitivity using clinically relevant experimental heat stress conditions; second, to identify molecular mechanisms that promote HCC cell survival to heat stress as potential candidate adjuvant therapeutic targets, with particular attention to the PI3K-AKT-mTOR pathway; and third, to investigate the biologic and prognostic significance of candidate pathways to human HCC. Here, MTOR is linked to hepatocellular carcinoma.