Abstract: Objective：To evaluate the safety and efficacy of combined endovascular brachytherapy (EVBT), transarterial chemoembolization (TACE), and sorafenib for the treatment of primary hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT). Methods：Sixty-eight primary HCC patients with MPVTT were included in the single-center retrospective study, who were unfit for surgical resection, percutaneous frequency ablation, and liver transplantation according to the BCLC classification. All patients had Child-Pugh classification grade A or B, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. The patients received either EVBT with stent placement, TACE, and sorafenib (group A, n=37), or TACE with sorafenib (group B, n=31). The time to progression (TTP) and overall survival (OS) were evaluated by propensity score analysis. Results：The 6-, 12-, and 24-mo survival rates were 88.9%, 54.3%, and 14.1% in group A, and 45.8%, 0, and 0 in group B, respectively. The median values of OS in group A were 12.3 and 10.3 months before and after matching respectively, which were longer than those in group B（5.2 and 6.0 months, P<0.001）. And the median values of TTP in group A were both 9.0 months before and after matching,which were longer than those in group B (both were 3.4 months before and after matching, P<0.001). Multivariate Cox analysis revealed that the EVBT combined with TACE and sorafenib strategy was an independent predictor of favorable OS (HR=0.18, P<0.001). Conclusions：EVBT combined with TACE and sorafenib might be a safe and effective palliative treatment option for HCC patients with MPVTT.