Inclusion Criteria:

1. Patient must have advanced hepatocellular carcinoma; fibrolamellar HCC is not allowed. Hepatocellular carcinoma will be confirmed by at least one of the following:
   1. Tissue diagnosis.
   2. The presence of one or more liver lesions measuring 2 cm in longest diameter, showing characteristic arterial enhancement and venous washout using arterial-phase contrast enhanced imaging, and a clinical history of cirrhosis.
2. Voluntary signed and dated institutional review board (IRB) approved informed consent form in accordance with regulatory and institutional guidelines.
3. Documented progression or intolerance to sorafenib as determined by the enrolling investigator:
4. Patient must have at least one measurable untreated lesion as per modified RECIST criteria. Measurable disease may include extrahepatic lesions. Abdominal imaging should employ a "liver protocol" image capture technique. The following are not considered measurable lesions: bone lesions, ascites, and pleural effusions. Prior RFA, PEI, or TACE of non-target lesions is allowed.
5. Time interval for last local therapy (radiofrequency ablation, percutaneous ethanol injection, radiotherapy, transarterial chemoembolization) more than 4 weeks prior to registration.
6. Life expectancy of at least 12 weeks.
7. 18 years of age or older.
8. ECOG performance status of 0-2.
9. Child-Pugh Cirrhotic Status A or B with a score of 7.
10. Acceptable liver function:
    1. Bilirubin ≤ 3 times upper limit of normal (CTCAE Grade 2 baseline).
    2. AST (SGOT), ALT (SGPT) 3 x ULN (CTCAE Grade 1 baseline).
11. Acceptable kidney function:
    1. Serum creatinine ≤ 1.5 XULN (CTCAE Grade 1 baseline).
12. Acceptable hematologic status:
    1. Absolute neutrophil count 1000 cells/mm3.
    2. Platelet count 75,000 (plt/mm3), (CTCAE Grade 1 baseline).
    3. Hemoglobin 9 g/dL.
13. Acceptable blood sugar control:
    1. Fasting glucose < 160 mg/dL (CTCAE grade 1 baseline).
14. Urinalysis: No clinically significant abnormalities.
15. INR < 1.7.
16. As determined by the treating investigator, the patient must have well-controlled blood pressure, defined as systolic blood pressure <150mmHg and/or diastolic blood pressure <100 mmHg for the majority of measurements.
17. A negative pregnancy test (only for WOCBP).
18. Willingness to use effective contraceptive methods during the study. If patient is female (or female partner of male subject), must be either not of childbearing potential (defined as postmenopausal for ≥ 1 year or surgically sterile) or is practicing two forms of contraception. Sexually active male participants must agree to use a physical barrier method (male latex rubber condom with or without spermicide).

Exclusion Criteria:

1. New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
2. Underlying psychiatric disorder requiring hospitalization within the last two years or a HADS score of 11 or more.
3. Clinically significant neurological disorder (Parkinson's disease, dementia, multiple sclerosis), as determined by the enrolling investigator.
4. Active, uncontrolled bacterial, viral or fungal infection, requiring systemic therapy.
5. Pregnant or nursing women. NOTE: Women of childbearing potential and men must agree to use adequate contraception or abstinence prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
6. Treatment with radiation therapy, surgery, or investigational therapy within one month prior to registration.
7. More than two lines of prior systemic therapy for HCC.
8. Unwillingness or inability to comply with procedures required in this protocol.
9. Known infection with HIV.
10. Hepatitis C on protease therapy.
11. Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator.
12. Patients who are receiving drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes that cannot be stopped at least 7 days or 5 half-lives (whichever is longer) before starting treatment with ABC294640 and either replaced with another appropriate medication or not given for the duration of the clinical study. (A list of commonly used drugs that are sensitive substrates of CYP450 1A2, 3A4, 2C9, 2C19 or 2D6, or strong inhibitors or inducers of all major CYP450 isozymes with the half-life of each drug identified, is included as an Appendix C).
13. A history of CTC Grade 3 bleeding esophageal or gastric varices within the past 2 months. Prior variceal bleed is permitted if patient has undergone banding or sclerotherapy and there has been no evidence of bleeding for 2 months. Patients at risk for varices (based on the following: known history of esophageal or gastric varices; evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices) will be screened (using either esophagogastroduodenoscopy (EGD) or capsule endoscopy) for esophageal varices, unless such screening has been performed in the past two years from study entry and the patient is receiving medical treatment for prophylaxis of variceal bleeding, such as non-selective beta blockade. If varices are identified that require intervention (banding), patient will not be eligible until varices are adequately treated. Patients presenting with gastric varices will not be eligible for the study.
14. Patients who are currently taking Coumadin or Coumadin derivatives.
15. Patients who are currently participating in any other clinical trial of an investigational product.
16. History of organ transplantation.
17. Other primary malignancy within past 5 years except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer.
18. Any other mental incapacitation or psychiatric illness that would preclude study participation, as determined by the enrolling investigator.
19. Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.