• Men and women ≥ 18 years old

• Patient should understand, sign, and date the written informed consent form prior to any investigation-specific procedures performed.

• Patient should be able to comply with investigational procedure, tissue and blood sample collection and willing to comply with investigation visits and procedures as per clinical investigation plan.

• Patients must have pathological confirmation of HCC.

• HCC classed Barcelona Clinic Liver Cancer (BCLC) stage C

• Patient should be considered as non resectable by Multidisciplinary Team and liver surgeon, and non-eligible for liver transplantation

• Patient should be eligible for 1st line Atezolizumab and Bevacizumab combination therapy. Patients previously treated by a local therapy are eligible.

• Patient with active intrahepatic HCC.

• Patients with or without active viral infection (i.e., HCV, HBV) are eligible. In case of active hepatitis B, the patient should be treated with an anti-HBV therapy during the investigational procedure.

• Patients should have measurable disease as defined by mRECIST criteria for response assessment.

• ECOG status of 0 or 1 (Appendix 2).

• Life expectancy of ≥ 12 weeks at the time of informed consent per Investigator assessment.

• Adequate organ function as defined by the following:

‣ White blood cells (WBCs) ≥ 2000/mL

⁃ Platelets ≥ 70 × 103/mL

⁃ Hemoglobin ≥ 8.0 g/dL

⁃ Creatinine \< 1.5 × ULN or creatinine clearance ≥ 40mL/min (Cockcroft-Gault formula)

⁃ ALT and AST ≤ 3 × ULN

⁃ Lipase and amylase ≤ 1.5 × ULN

⁃ Total bilirubin ≤ 1.5 × ULN

• Child-Pugh A, Without history of encephalopathy or clinically significant ascites

• Women of childbearing potential (WOCBP) must have a negative urine or serum β-HCG pregnancy test within 7 days prior registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Sexually active female patients must agree to use two methods of effective contraception\*, one of them being a barrier method, or to abstain from sexual activity during the clinical investigation and for at least 6 months after last drug administration of the investigational procedure or must refrain from heterosexual activity during this same period\*\*.

• \* Acceptable contraceptive methods include single or combined contraceptive methods that result in a failure rate of \< 1% per year, such as: tubal ligation, male sterilization, hormonal implants, proper use of combined oral or injected hormonal methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of \< 1% per year. Barrier methods must always be supplemented with the use of a spermicide.

• \*\* Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

• Sexually active males patients must agree to use condom during the clinical investigation and for at least 7 months after the last drug administration of the investigational procedure. Also, it is recommended the childbearing potential female partner uses a highly effective method of contraception for the same duration.

• Patients shall be eligible to undergo pre-treatment and on-treatment tumor biopsies. Patients who either do not consent to a pre-treatment tumor biopsy or do not have accessible lesions will not be eligible.

• Patients must be affiliated to a social security system or beneficiary of the same