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Most adverse events were grades 1-2, and the majority of patients tolerated the side effects. Our study confirms the efficacy and safety of lenvatinib as second-line and later line treatment for patients with unresectable HCC who received sorafenib in clinical practice. 400 ng/mL was an independent prognostic factor of worse PFS and OS. The clinical outcomes of lenvatinib therapy as second-line, third-line, or fourth line and later line treatment were similar, and previous response to sorafenib could predict the response to subsequent l