This is an open labeled, multiple centers, two countries (Taiwan and Korea) non-comparative phase I trial in patients with hepatocellular carcinoma. In phase I part, a maximum of 18 patients will be recruited in this study.

After screening, each eligible patient will undergo a treatment of OBP-301 within 14 days and will automatically enter follow-up period.

The follow-up period is up to 12 weeks after the last injection in the phase I part.

Each patient will return for follow-up visit weekly in the first month after the last injection, and then every 4 weeks up to the end of follow-up period.

Inclusion Criteria:

1. Patients aged 18 to 65 years (19 to 65 years in Korea), either sex

2. Patients diagnosed with hepatocellular carcinoma. The diagnosis of HCC (hepatocellular carcinoma) should be established by cytology or histopathology

3. Patients who have unresectable HCC and meet all of the following conditions:

   • Barcelona Clinic Liver Cancer (BCLC) stage B or C
   • TransAarterial ChemoEmbolization (TACE) refractory in discretion of the investigators, or TACE unsuitable (such as but not limited to portal vein thrombosis)
   • Local ablative treatment (such as percutaneous ethanol injection, radiofrequency ablation, etc) unsuitable
   • Sorafenib failure, intolerable or ineligible

4. Patients must have at least one lesion that can be accurately measured in at least one dimension as 1 cm or more and the lesion must be suitable for repeat measurement

5. Patients who have Child-Pugh's Score no greater than 7, and have no ascites

6. Patients who have all the conditions below at screening:

   serum ALT (Alanine Aminotransferase) level (GPT) less than 2.5 x UNL

   • serum AST (Aspartate Aminotransferase) level (GOT) less than 2.5 x UNL
   • WBC (white blood cell) greater than or equal to 3,000 / microliter
   • Serum creatinine less than or equal to 1.5 x UNL
   • activated partial thromboplastin time (APTT) <1.5 x UNL

7. Platelet count correctable to greater than or equal to 80,000 / microliter

8. prothrombin time-international normalized ratio (PT-INR) correctable to less than 1.5

9. Patients who have life expectancy longer than 12 weeks

Exclusion Criteria:

1. Patients who have had chemotherapy within last three weeks (6 weeks for nitrosourea or Mitomycin-C) prior to dosing
2. Patients who have had radiotherapy to tumor site within the last four weeks prior to dosing and with documentation of subsequent tumor growth at this site
3. Patients who have received other investigational or antineoplastic medication within the last four weeks prior to dosing
4. Patients who had history of esophageal variceal bleeding within eight weeks prior to study entry
5. Patients who have uncontrolled diabetes, active or chronic infection, including HIV, except for asymptomatic bacterial colonization, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
6. Patients who had acute viral infection syndrome diagnosed within the last two weeks
7. Patients who have concomitant hematological malignancy (e.g. acute lymphocytic leukemia, non-Hodgkin's lymphoma)
8. Patients who have active rheumatoid arthritis or other autoimmune disease.
9. Patients who have current requirement for chronic systemic immunosuppressive medication including any dose of glucocorticoid or cyclosporin, or chronic use of any such medication within the last four weeks Note: Course of glucocorticoid therapy less than 10 days duration is allowed (e.g. for nausea control)
10. Patients with organ transplants (may require prolonged immunosuppressive therapy)
11. Patients who had prior participation in any research protocol which involved administration of adenovirus vectors
12. Patients received any immune-related related related related related blood products, such as immunoglobulin in the prior 3 months
13. Patients who have uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
14. Psychiatric, addictive, or any disorder which compromises ability to give truly informed consent for participation in this study or adequate compliance
15. Female patients that are pregnant or on breast-feeding
16. Patients who receive anti-platelet agents or anti-coagulation agents (e.g. Heparin, warfarin, aspirin, ticlopidine, clopidogrel, dipyridamole and so on).