Considering the crucial effect of SOX12‐CCL22/CCR4 and SOX12‐PD‐L1 axis on the TIME remodeling and the HCC progression and metastasis, we evaluated the antitumor effect of combining CCR4 inhibitor (C‐021) with anti‐PD‐L1 in HCC models. The gene discussed is SOX12; the disease is hepatocellular carcinoma.