Herein, we present the final safety and antitumor activity results of the investigator-initiated, first-in-human, and exploratory clinical study, which tests the combination of lenvatinib plus EGFR inhibitor gefitinib in 30 EGFRhigh HCC patients, who expressed high protein level of EGFR and showed disease progression upon lenvatinib treatment. Here, EGFR is linked to hepatocellular carcinoma.