This is a prospective study to investigate the biomarkers in predicting treatment outcome and toxicity in hepatocellular carcinoma (HCC) patients receiving immune checkpoint inhibitors with or without stereotactic body radiotherapy (SBRT).

Inclusion Criteria:

First Cohort (SBRT+IO):

1. Unresectable HCC confirmed by multi-disciplinary team
2. Tumor size 5-15cm
3. Number of lesion(s) ≤ 3
4. No main portal vein or inferior vena cava thrombosis
5. ECOG performance status 0-1
6. Child-Pugh class A-B7
7. Liver volume minus gross tumor volume > 700ml
8. Adequate organ function
9. No prior systemic therapy, immunotherapy, TACE, radiotherapy, or radio-embolization

Second Cohort (IO alone):

1. BCLC stage C HCC
2. ECOG performance status 0-1
3. Child-Pugh class A5-B9
4. Adequate organ function

Exclusion Criteria:

1. Based on the inclusion criteria above. Any eligibility factors that do not fit the inclusion criteria will be considered as ineligible subjects.

Based on the inclusion criteria above. Any eligibility factors that do not fit the inclusion criteria will be considered as ineligible subjects.