Treatment of intermediate and advanced HCC has introduced new options, such as targeted agents for lenvatinib and immunotherapy with programmed cell death protein 1 (PD-1)/ligand for PD-1 (PD-L1) inhibitors, but not all patients will benefit; development of drug resistance during treatment may limit therapeutic options and lead to a poor prognosis. The gene discussed is PDCD1; the disease is hepatocellular carcinoma.