There are currently few data on immune checkpoint inhibitors (ICIs) combined with molecular targeted agent (MTA) in the second-line treatment of advanced HCC, therefore, we analyzed the efficacy and safety of the patients who received PD-1 inhibitors combined with lenvatinib (PL) versus those who received PD-1 inhibitors plus regorafenib (PR) after sorafenib resistance. The gene discussed is PDCD1; the disease is hepatocellular carcinoma.