• Capable of giving written informed consent and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.

• Age ≥ 18 years at time of study entry.

• Body weight \> 30 kg.

• Multinodular or large, solitary HCC, not eligible for resection or local ablation.

• Histologically confirmed diagnosis of HCC.

• Scheduled to receive locoregional therapy as standard of care.

• At least one measurable site of disease as defined by RECIST 1.1criteria with spiral CT scan or MRI.

• No prior systemic anti-cancer therapy.

• Child-Pugh A.

⁃ Performance status (PS) ≤ 1 (ECOG scale).

⁃ Life expectancy of at least 12 weeks.

⁃ Adequate blood count, liver-enzymes, and renal function:

∙ Hemoglobin ≥ 9.0 g/dL, absolute neutrophil count ANC ≥1.5 (or 1.0) x (\> 1500 per mm\^3), platelets ≥100 (or 75) x 10\^9/L (\>75,000 per mm\^3);

‣ Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN);

‣ AST (SGOT), ALT (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are present, in which case it must be ≤5x ULN;

‣ International normalized ratio (INR) ≤ 1.25.

⁃ Albumin ≥ 31 g/dL.

⁃ Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine clearance CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.

⁃ Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial and must use two effective forms of contraception if sexually active.

⁃ Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving IMP and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational products (Durvalumab and Tremelimumab). Women who are not of childbearing potential (i.e. who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception).

⁃ If patient has concurrent Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection, meets the following criteria:

∙ Patients with HBV or HCV infection should be monitored for viral levels during study participation;

‣ Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should have HBV DNA \< 100 IU/ml and should be managed per local treatment guidelines. Controlled (treated) hepatitis B subjects will be allowed if they started treatment at the time point of enrollment into the study by the latest and treatment is continued during study participation and for ≥ 6 months after end of study treatment;

‣ HCV patients with advanced HCC are mostly not treated for their HCV infection. However, patients treated for HCV are considered suitable for inclusion if antiviral therapy has been completed prior to first administration of study drug.

⁃ Subject is willing and able to comply with the protocol for the duration of the study including