Background: The combination of transcatheter arterial chemoembolization (TACE) plus Lenvatinib prolonged progression-free survival (PFS) and overall survival (OS) than Lenvatinib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of Lenvatinib plus monoclonal antibody against programmed cell death 1 (anti-PD1) and TACE for patients with advanced HCC. Methods: Pts with advanced HCC who treated with Lenvatinib plus anti-PD1 and TACE were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety. Consecutive pts were identified from September 2021 to August 2023.The Patients were included based on the following chief eligibility criteria. After signing the informed consent form, patients received sequential treatment with TACE in combination with Lenvatinib and tislelizumab. The anti-PD1 were recommended to be used continually every 3 weeks until disease progression, or intolerable toxicity. Lenvatinib was recommended to be used continually every day until disease progression, or intolerable toxicity. Follow up TACE should be given according to the patient's condition, no more than 3 times. Results: Between Sep. 2021 to Aug. 2023, 45 were enrolled. All pts received at least one dose of study treatment. The median age was 56 years(range34,73), 4 of the pts are BCLC-B stage, 41 of the pts are BCLC-C stage.Progression occurred in 8 of 45 patients and 14 patients died. The median PFS was 13.4 months (95% CI: 10.9-15.8 months) and the median OS was 20 months (95% CI: 9.8-30.4months). Of the 45 patients, a total of 3 (6.7%) patients achieved complete response (CR), and these 3 patients were treated with surgical resection. Partial Response (PR) was achieved in 12 patients (20%), Stable Disease (SD) in 22 pts (33.3%), Progressive Disease (PD) in 8 pts (17.8%), and Objective Response Rate (ORR) in patients. The Objective Response Rate (ORR) was 33.3% and the Disease Control Rate (DCR) was 82.2%.Treatment-related adverse events included increased AST 44.4%(20/45), increased ALT 51.1%(23), increased total bilirubin 42.2%(19/45), rash 44.4%(20/45), pruritus 42.2%(19/45), gastrointestinal reaction 33.3%(15/45), abdominal pain 24.4%(11/45), sensory abnormality 20%(9/45), and arthralgias 4.4%(2/45), etc., and Grade 3 Adverse events were increased ALT 2.2%(1/45), increased AST 4.4%(2/45), increased total bilirubin 2.2%(1/45), rash 2.2%(1/45), and gastrointestinal reaction 2.2%(1/45).No grade 4 or above adverse events occurred. Conclusions: In this study, TACE plus anti-PD1 and targeted therapies showed favorable efficacy and manageability in patients with advanced HCC. Toxicity was manageable with a low incidence of grade 3-4 adverse events. There were no unexpected safety signals.