Taken together, our findings have identified sulfarotene as a potentially effective agent that selectively targets HCC tumor-repopulating cells, which in many aspects resemble cancer stem cells and contribute significantly to the recurrence and drug resistance of HCC, and highlights SOS2 as a critical new oncogenic factor in association with RARα and RAS that together form a novel signal nexus in HCC. The gene discussed is RARA; the disease is hepatocellular carcinoma.