Lenvatinib, a tyrosine kinase inhibitor, serves as a first‐line treatment for patients with advanced HCC.[21] However, it can induce treatment resistance through activation of bypass signaling pathways, including the EGFR and FGFR pathways.[22] We next treated the mice harboring Huh7 cell‐derived HCC tumors with a combination of lenvatinib and the Insig1/2 loop 1 peptide, which exhibited an additive inhibition of tumor growth (Figure 3a–d) and prolonged mouse survival time (Figure 3e) compared with lenvatinib or the Insig1/2 loop 1 peptide alone. This evidence concerns the gene INSIG1 and hepatocellular carcinoma.