The goal of this phase 2 prospective clinical trial is to learn about the efficacy and safety of stereotactic body radiation therapy (SBRT) plus immunotherapy and targeted therapy in patients with unresectable or oligometastatic hepatocellular carcinoma (HCC).

The main question to answer is: Whether combing SBRT with immunotherapy and targeted therapy could prolong PFS. Participants will receive SBRT to all visible lesions and concurrent systemic immunotherapy and targeted therapy.

Inclusion Criteria:

• age ≥ 18 years
• Eastern Cooperative Oncology Group performance status of 0-1
• clinical or pathological diagnosis of HCC
• with unresectable locally advanced or oligometastatic HCC (metastatic lesions ≤ 5, metastatic organs ≤ 3, may involve extrahepatic lymph nodes or distant organs apart from brain)
• at least one measurable lesion according to mRECIST criteria
• all lesions could be included in radiation target volume
• Child-Pugh A or B (7 scores) liver function
• patients are allowed to receive systemic therapy previously other than tislelizumab plus regorafenib
• adequate hematological and renal function
• life expectancy ≥ 3 months；
• willing to participate in the study and give written informed consent

Exclusion Criteria:

• a history of liver transplantation
• with severe cirrhosis complications, including a history of esophagogastric variceal bleeding, hepatic encephalopathy, and massive ascites
• with active autoimmune diseases or a history of autoimmune disease
• with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
• allergic to the ingredient of tislelizumab or regorafenib
• with recurrent lesions treated with radiotherapy previously
• prescribed radiation does could not be delivered due to dose limits to organs at risk (OAR)
• intolerable to radiation or systemic treatment because of cardiac insufficiency, uncontrolled high blood pressure
• a history of other malignancies, except cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix