In the present study, we characterize the levels of the members of the six major classes of sphingolipids and phospholipids [Cer, PC, lysophosphatidylcholine (LPC), PE, lysophosphatidylethanolamine (LPE), SM] in two HCC cell lines: HepG2 and Huh-7 were either silenced for the expression of histone variant macroH2A1, which contributes to transform them in liver CSC-like cells [17,18,19], or silenced for the expression of focal adhesion tyrosine kinase (FAK), which in turn is capable of inhibiting their aggressiveness and stemness [21,22]. This evidence concerns the gene PTK2 and hepatocellular carcinoma.