These results indicate that patients with high PIVKA‐II expression are more likely to be resistant to anti‐PD‐1 plus lenvatinib, and pre‐treatment peripheral blood PIVKA‐II levels may serve as a crucial indicator for predicting the efficacy of anti‐PD‐1 plus lenvatinib therapy in HCC. This evidence concerns the gene PDCD1 and hepatocellular carcinoma.