The purpose of this pilot safety study is to evaluate the safety and tolerability of JX-594 (Pexa-Vec) administered intravenously and intratumorally prior to standard sorafenib therapy.

Inclusion Criteria:

• Histological confirmation or clinical/laboratory diagnosis of primary hepatocellular carcinoma (HCC)
• Cancer is not surgically resectable for cure
• Child Pugh A or B
• Performance Score: KPS score of ≥ 70
• Platelet count ≥ 50,000 plts/mm3
• Total bilirubin ≤ 2.5 x ULN
• AST, ALT < 5.0 x ULN
• Acceptable coagulation status: INR ≤ 1.5 x ULN
• Acceptable kidney function: Serum creatinine < 2.0 mg/dL
• Sorafenib naive or refractory to sorafenib therapy Tumor Status: At least one intrahepatic tumor, and at least ≥50% of the total intrahepatic viable tumor mass, measurable by CT and injectable under imaging-guidance (note: injected and/or viable tumors must be previously untreated or ≥20% increase in size since preceding local-regional treatment).

Exclusion Criteria:

• Known contraindications to sorafenib
• Pregnant or nursing an infant
• Significant immunodeficiency due to underlying illness (e.g. hematological malignancies, congenital immunodeficiencies and/or HIV infection/AIDS) and/or medication (e.g. high-dose systemic corticosteroids)
• History of exfoliative skin condition (e.g. severe eczema, ectopic dermatitis, or similar skin disorder) that at some stage has required systemic therapy
• Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions
• Severe or unstable cardiac disease
• Current, known CNS malignancy
• Use of anti-platelet or anti-coagulation medication
• Use of the following anti-viral agents: ribavirin, adefovir, cidofovir (within 7 days prior to the first treatment), and PEG-IFN (within 14 days prior to the first treatment).
• Patients with household contacts who meet any of these criteria unless alternate living arrangements can be made during the patient's active dosing period and for 7 days following the last dose of study medication:
• Pregnant or nursing an infant
• Children < 12 months old
• History of exfoliative skin condition that at some stage has required systemic therapy
• Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication