This is a prospective, multi-center, open-label study to evaluate the effectiveness and safety of Eye90 microspheres® in the treatment of subjects with unresectable Hepatocellular Carcinoma (HCC). Eye90 microspheres is a medical device containing yttrium-90 (Y-90), a radioactive material, and provides local radiation brachytherapy for the treatment of liver tumors.

Inclusion Criteria:

• Must have a confirmed diagnosis of HCC by imaging confirmation with Liver Imaging Reporting and Data System (LIRADS) category 5 or confirmation of HCC via biopsy.
• No extra hepatic disease.
• Up to 3 lesions with at least one lesion ≥ 2 cm in diameter (long axis) measurable by computed tomography (CT), CBCT, or MRI. At least one lesion must be identified as a target lesion as defined by mRECIST.
• Maximal single lesion size of ≤ 8 cm and sum of the maximal tumor dimensions of ≤ 12 cm with the entire tumor burden expected to be treatable within the perfused volume.
• Intent to treat all lesions within a single session.
• Hypervascular on CBCT, CT, or MRI.
• Evidence that > 33% of the total liver volume is disease-free and will be spared Eye90 treatment.
• Life expectancy of ≥ 6 months.
• ≥ 18 years old at the time of informed consent

Exclusion Criteria:

• Platelet count <50,000/microliter or prothrombin (PT) activity > 50% normal.
• Hemoglobin ≤ 8.5 g/dL (subjects that are non-responders to transfusion or medical management must be excluded).
• INR > 1.7 (if anticoagulated, reversal must be achieved prior to any angiographic procedures).
• ALT > 5x upper limit.
• AST > 5x upper limit.
• Bilirubin ≥ 2.0 mg/dL.
• eGFR ≤ 50 mL/min/BSA.
• Macrovascular invasion.
• Incompetent biliary duct system, prior biliary intervention, or a compromised Ampulla of Vater.
• Estimated lung dose > 30 Gy as calculated using the lung shunt fraction and partition model.