Introduction: Current clinical guidelines recommend systematic antitumor therapy as the primary treatment option for patients with stage IIIb hepatocellular carcinoma (HCC) based on the China liver cancer staging (CNLC) criteria. Several different targeted therapeutics have been applied in combination with immunotherapeutic regimens to date in patients with advanced HCC. The present study was developed to evaluate the relative safety and efficacy of hepatectomy in combination with targeted apatinib treatment and immunotherapeutic camrelizumab treatment CNLC-IIIb stage HCC patients with the goal of providing evidence regarding the potential value of this therapeutic regimen in individuals diagnosed with advanced HCC. Methods and analysis: This is a single-arm multicenter clinical trial in which patients undergo hepatectomy in combination with targeted treatment (apatinib) and immunotherapy (camrelizumab). Patients will undergo follow-up every 2-3 months following treatment initiation to record any evidence of disease progression and adverse event incidence for a minimum of 24 months following the discontinuation of treatment until reaching study endpoint events or trial termination. The primary endpoint for this study is patient mortality. Ethics and dissemination: This study protocol was approved by the Ethics Committee of the Guangxi Medical University Cancer Hospital for Human Study (reference number KS2022[124]). The results of this study will be submitted for publication in a peer-reviewed journal. Trial registration number: NCT05062837. Strengths and limitations of this study: 1. This study will be the first to assess the relative safety and efficacy of hepatectomy combined with targeted and immunotherapeutic treatment in CNLC-IIIb HCC patients. 2. As a multicenter study, the results of this analysis will be representative, generalizable, and reliable. 3. As this study will entail a prolonged follow-up period, it is critical that participants be thoroughly informed prior to enrollment, with individuals exhibiting high compliance being chosen for study inclusion.

The authors have declared no competing interest.

NCT05062837

The experiment was established and overseen by physicians at Guangxi Medical University's Affiliated Cancer Hospital, and Jiangsu Hengrui Pharmaceutical Company Limited provided both the camrelizumab and apatinib used in the trial free of charge, with the patients covering all other expenditures.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics Committee of the Guangxi Medical University Cancer Hospital gave ethical approval for this work

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All data produced in the present study are available upon reasonable request to the authors