To investigate the mechanisms of lenvatinib resistance in HCC, we developed a lenvatinib-resistant cell lines,MHCC97H-R (97H-R), by incubating them with 5 μM lenvatinib in 6-well plates. The concentration was subsequently increased by 2.5 μM each week. These cells will be injected subcutaneously into nude mice and continued to be administered lenvatinib through in vivo administration. Harvest when it is determined that lenvatinib resistance has emerged. These cell will ejcted We conducted proteomic sequencing analyses of a lenvatinib-resistant cell line and wild cell line, identifying critical factors associated with lenvatinib resistance in HCC.