• Histologically confirmed HCC (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects (presence of arterial hypervascularity with venous washout). For subjects without cirrhosis, histological confirmation is mandatory.

• Participants must have resectable disease. Those patients must have preserved liver function (Child A) and with either AJCC stage IA, IB, II, and IIIA or BCLC stage 0 or stage A disease. The determination of resectability will ultimately lie in the clinical judgment of the treating investigator and surgical oncologist involved in the care of the patient.

• Participants must be treatment naïve for HCC.

• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of tremelimumab, durvalumab, and SIRT in participants \<18 years of age, children are excluded from this study.

• Measurable disease per RECIST 1.1 criteria.

• ECOG performance status ≤ 1 (see Appendix A).

• Body weight \>30 kg.

• Participants must have adequate organ and marrow function as defined below:

‣ Hemoglobin ≥ 9.0 g/dL

⁃ Absolute Neutrophil Count (ANC) ≥ 1,000 /mcL

⁃ Platelets ≥ 80,000 /mcL

⁃ Total Bilirubin ≤ 2.0 mg/dL

⁃ AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional upper limit of normal (ULN)

⁃ Measured Creatinine Clearance \> 40 mL/min by 24-hour urine collection, or

⁃ Calculated Creatinine Clearance (CL) \> 40 mL/min by the Cockcroft-Gault Formula (Cockcroft Gault 1976):

• Males: Creatinine CL (mL/min) = (weight (kg) × (140 - Age)) / (72 × serum creatinine (mg/dL))

∙ Females: Creatinine CL (mL/min) = (weight (kg) × (140 - Age) / (72 × serum creatinine (mg/dL))) × 0.85

• Women of childbearing potential (WOCBP, refer to Section 5.4) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) obtained during the trial screening period.

• Men and WOCBP must agree to follow the protocol instructions for acceptable method(s) of contraception for the duration of trial treatment and for a total of 5 months post-treatment completion. Refer to Section 5.4.

• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen as assessed by the treating investigator are eligible for this trial.

• Ability to understand and the willingness to sign a written informed consent document.