The proposed study is a single site, prospective, randomized phase 2 study to evaluate the efficacy and tolerability transarterial radioembolization (TARE) versus stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. The SBRT arm of the trial will involve standard SBRT delivered over 3-5 fractions as tolerated with dose/total therapy adjusted as needed for safety. The TARE arm of the trial will involve a planning arteriogram followed by selective transarterial delivery of Yttrium-90 into the segmental (≤2) artery supplying the tumor. Administered activity will be an amount prescribed to deliver a dose ≥200 Gy to the perfused tissue. The primary endpoint is the rate of re-treatment of the index lesion over 12 months.

Inclusion Criteria:

• Ability to provide written informed consent and HIPAA authorization
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged ≥ 18 years at time of informed consent
• No more than 3 lesions of HCC evaluated to be eligible for TARE or SBRT at multidisciplinary tumor board
• Childs-Pugh score ≤ 8
• ECOG performance status ≤2
• Adequate organ function defined as:
• serum bilirubin < 4.0 mg/dL ,
• albumin > 2 g/dL

Exclusion Criteria:

• Any prior SBRT or radioembolization to the target tumor
• Macrovascular invasion
• Planned or recommended systemic therapy as consolidation
• Pregnancy or lactation: Women of childbearing potential must have a negative pregnancy test within 14 days of protocol registration.
• Known severe allergic reaction (anaphylaxis) to iodinated contrast Coagulopathy that the provider deems would be unsafe for transarterial therapy