Inclusion Criteria

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

- Tumor progression during or after at least one prior HCC treatment regimen (Note: If
standard HCC therapies are either medically contraindicated or patient has refused
those treatments, the patient may be eligible for this study)

- Performance Score: KPS score of ≥ 70

- Anticipated survival of at least 16 weeks

- Total bilirubin ≤ 2.5 x ULN

- AST, ALT < 5.0 x ULN

- WBC > 2,500 cells/mm3 and < 50,000 cells/mm3 (GCSF treatment allowed)

- ANC > 1,250 cells/mm3 (GCSF treatment allowed)

- Hemoglobin ≥ 9 g/dL (RBC transfusion allowed)

- Platelet count ≥ 50,000 plts/mm3

- Acceptable coagulation status: INR ≤ 1.5 x ULN

- Acceptable kidney function: Serum creatinine < 2.0 mg/dL

- If patients are diabetic or have a screening random glucose > 160 mg/dL, a fasting
glucose must be done and patients must be WNL or Grade 1 in order to be eligible for
the study

- For patients who are sexually active: able and willing to abstain from sex during
treatment period and for 3 weeks following treatment, and use an acceptable method of
birth control for 3 months after last injection with JX-594

- Able/willing to sign an IRB/IEC/REB-approved written consent form

- Able and willing to comply with study procedures and follow-up examinations,
including compliance with the "Infection Control Guidelines for Patients" (in written
consent form)

Exclusion Criteria:

- Current, known extra-hepatic tumors that, in the investigator's medical opinion, are
likely to result in significant morbidity or mortality within the next 16 weeks.

- Pregnant or nursing an infant

- Known infection with HIV

- Clinically significant active infection or uncontrolled medical condition considered
high risk for investigational new drug treatment

- 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

- Liver tumors in a location that would potentially result in significant clinical
adverse effects if post-treatment tumor swelling were to occur (e.g. tumors impinging
on the biliary tract that could affect drainage)

- Severe or unstable cardiac disease

- Current, known CNS malignancy

- Anti-cancer therapy (e.g. RFA, TACE, PEIT, radioembolization, chemotherapy, surgery,
or an investigational drug, etc.) within 4 weeks prior to first treatment

- Absolute contraindication to undergoing MRI scanning

- Experienced a severe systemic reaction or side-effect as a result of a previous
smallpox vaccination

- 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).

- Inability or unwillingness to give informed consent or comply with the procedures
required in the protocol

- 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