Compared with already known biomarkers such as AFP, GPC3 and DCP, our study constructed a novel cuproptosis-related prognostic signature (Cu-PS) that might be a useful biomarker for predicting immunotherapy response and enhancing diagnosis and treatment of HCC, which indicates that cuproptosis is associated with the TIME and HCC prognosis. The gene discussed is AFP; the disease is hepatocellular carcinoma.