This study aims to evaluate the safety and effectiveness of a combined treatment for patients with unresectable hepatocellular carcinoma (HCC), a type of liver cancer that cannot be removed by surgery. The treatment includes transarterial chemoembolization (TACE), which delivers chemotherapy directly into the liver tumor, together with low-dose bevacizumab and atezolizumab, two medicines that help the immune system fight cancer and inhibit tumor blood vessel growth.

All participants in this study will receive the same combination treatment as their first-line therapy. The study will observe how well the tumor responds, how long the treatment can control the cancer, and what side effects may occur. The goal is to learn whether this combined approach can provide clinical benefit and improve outcomes for patients with advanced, unresectable liver cancer.

Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage, when surgical treatment is no longer possible. Transarterial chemoembolization (TACE) is widely used for locoregional control, but many patients eventually experience tumor progression due to treatment-related hypoxia and activation of pro-angiogenic pathways. Combining TACE with systemic therapies that block angiogenesis and enhance antitumor immunity may help overcome these limitations.

Bevacizumab, an anti-VEGF antibody, reduces tumor angiogenesis and may counteract the surge in VEGF that occurs after TACE. Atezolizumab, an immune checkpoint inhibitor, strengthens the immune response against cancer cells. Using low-dose bevacizumab together with atezolizumab may help maximize immunotherapy benefit while minimizing toxicity, especially when administered after TACE.

This single-arm Phase II study is designed to investigate whether integrating TACE with low-dose bevacizumab and atezolizumab as first-line treatment can improve clinical outcomes in patients with unresectable HCC. The study will evaluate tumor control, treatment duration, and safety in real-world clinical settings. The findings may provide evidence to support a multimodal treatment strategy that targets both the tumor vasculature and the immune microenvironment, potentially offering a more effective option for patients with advanced liver cancer.

Inclusion Criteria:

• Age between18 and 75 years;
• Has a diagnosis of HCC confirmed by radiology, histology, or cytology;
• Child-Pugh class A;
• Eastern Cooperative Group performance status (ECOG) score of 0-1;
• No prior systemic therapy for HCC.
• Adequate hematologic and end-organ function;
• At least one measurable intrahepatic target lesion.

Exclusion Criteria:

• Diffuse HCC;
• Cholangiocarcinoma, fibrolamellar, sarcomatoid hepatocellular carcinoma, and mixed hepatocellular/cholangiocarcinoma subtypes (confirmed by histology, or pathology) are not eligible;
• Evidence of extrahepatic spread (EHS);
• Any condition representing a contraindication to TACE or I-125 seeds brachytherapy as determined by the investigators;
• Evidence or history of bleeding diathesis or any hemorrhage or bleeding event >CTCAE grade 3 within 4 weeks prior to randomization;
• Active or history of autoimmune disease or immune deficiency;
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding;
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment;
• Evidence of bleeding diathesis or significant coagulopathy;
• Pregnant or breastfeeding females;
• Significant cardiovascular disease;
• Severe infection, such as active tuberculosis;
• Serious medical comorbidities;
• History of organ or cells transplantation;
• History of other uncurable malignancies.

Individual participant data (IPD) may be shared upon reasonable request. Any data sharing will be discussed and agreed upon with the corresponding author to ensure that it complies with ethical, regulatory, and institutional requirements.