In HCC, ICB combined with C‐021, a small molecule inhibitor targeting CCR4, or neutralizing antibody against CCR4, exhibits a significant antitumor effect.[8, 11] Our intrahepatic orthotopic HCC models and DEN/CCl4‐treated Sox12HepOE model demonstrated a significant advantage of C‐021 combined with anti‐PD‐L1 treatment in restoring antitumor immunity and suppressing the SOX12‐mediated HCC progression and metastasis. The gene discussed is CCR4; the disease is hepatocellular carcinoma.