When multi-kinase inhibitors based therapies (sorafenib and regorafenib) are limited in late-stage liver cancer patients, there is no alternative options. PD-1 blockade has became a promising immunotherapeutic strategy in many cancers. While it showed limited efficacy in liver cancer. Polyinosinic-polycytidylic acid (PolyIC) has been widely studied as a new anti-tumor drug and recent study showed that polyIC and PD-L1 mAb has a quite synergetic effect on the hepatocellular carcinoma (HCC). This study is aimed to evaluate the safety and efficacy of the combination of PolyIC and PD-1 mAb in unresectable late-stage HCC patients.

Nowadays, primary liver cancer, especially hepatocellular carcinoma (HCC) has become the second leading cause of cancer-related death. Unfortunately, the therapeutic strategies are still limited for HCC. For HCC patients at advanced stage, up to now, sorafenib and regorafenib are applied for palliative therapy to prolong the patients' life. PD-1 blockade has became a promising immunotherapeutic strategy in many cancers. While it showed limited efficacy in liver cancer. Polyinosinic-polycytidylic acid (PolyIC) has been widely studied as a new anti-tumor drug and recent study showed that polyIC and PD-L1 mAb has a quite synergetic effect on the treatment of HCC. This study is aimed to evaluate the safety and efficacy of the combination of PolyIC and PD-1 mAb in unresectable late-stage HCC patients.

Inclusion Criteria:

1. Hepatocellular carcinoma with imaging diagnosis, in barcelona stage C, or stage B but resistant/recurrent to prior local treatment (e.g., TACE).

2. Eastern cooperative oncology group physical fitness score: 0-2.

3. Predicted survival time≥3 months.

4. Liver function of Child-Pugh A-B, no hepatic encephalopathy or physical examined ascites.

5. Routine blood tests were in accordance with the following criteria:

   White blood cell (WBC)≥2.0x10^9/L, Neutrophil≥1.0x10^9/L, platelet (PLT)≥50x10^9/L, hemoglobin (HB)≥80 g/dL, creatinine≤1.5xULN (upper limit of normal value), Alanine transaminase (ALT) and aspartate aminotransferase (AST)≤5xULN, total bilirubin (TB)≤51.3umol/L, international normalized ratio (INR) or prothrombin time (PT)≤1.7xULN, activated partial thromboplastin time (APTT)≤1.5xULN, serum albumin≥28g/L

6. Patients will be informed consent, and understand and are willing to cooperate with the trial and sign related documents.

Exclusion Criteria:

1. Has a history of malignant tumor in last 2 years, except basal and skin squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, superficial bladder cancer and carcinoma in situ of breast.
2. Received the treatment of polyIC or immune checkpoint inhibitors (e.g., PD-1/PD-L1 mAb or CTLA-4 mAb) in last 2 years.
3. Received the therapies of multi-kinase inhibitors (e.g., sorafenib, regorafenib), systemic chemotherapy, local therapy (e.g., TACE, radiotherapy), vaccination, immunomodulating therapy （e.g., interleukins, thymosin） or any other clinical trial in last 4 weeks.
4. Received any corticosterone or immunosuppressive drug in last 2 weeks.
5. Toxicity induced by previous anti-tumor therapies has not returned to the status of baseline or stability.
6. HIV positive (including previous anti-retroviral therapy), active HCV infection or active syphilis.
7. Any severe liver disease (e.g., severe liver cirrhosis, severe liver adenoma)
8. Any active or recurrent autoimmune disease.
9. Any interstitial pneumonia, non-infectious pneumonia, or uncontrolled systemic disease (e.g., uncontrolled hypertension or diabetes).
10. Severe cardiovascular risk factors.
11. Has a history of allogeneic stem cell transplantation or organ transplantation.
12. Imaging confirmed brain or meninges metastases.
13. Has the plan of pregnancy, or lactation.
14. Any kind of psychiatric disease or laboratory test abnormality that may result in the subject's failure to fully comply with the laboratory protocol.