Inclusion Criteria:

- Meets 1 of the following criteria:

- Histologically or cytologically confirmed hepatocellular carcinoma

- Serum alpha fetoprotein > 1000ng/dL with characteristic imaging findings coupled
with the appropriate clinical scenario (i.e., chronic hepatitis and/or
cirrhosis)

- Child's A or B cirrhosis allowed

- If Child's B cirrhosis is present, the patient may not have
significant encephalopathy or ascites that requires paracentesis and
must meet laboratory criteria (i.e., well-compensated Child's B)

- Metastatic disease (including any proven lymph node metastases) or localized disease
not amenable to potentially curative transplant/locoregional/surgical therapy as
determined by a qualified surgeon or tumor board

- Measurable disease, defined as at least one unidimensionally measurable ≥ 20 mm by
conventional techniques or ≥ 10 mm by spiral CT scan

- No known brain metastases

- ECOG performance status ≤ 2

- Life expectancy > 3 months

- Leukocytes ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,500/mm³

- Platelets ≥ 75,000/mm³

- Total bilirubin < 2 times upper limit of normal (ULN)

- AST/ALT < 5 times ULN

- Creatinine < 1.5 mg/dL or creatinine clearance ≥ 60 mL/min

- INR < 1.4

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception before, during, and for 4 weeks
after completion of study treatment

- Willing to undergo protocol-required tumor biopsies (patients must also be able to
have any anticoagulation held for an appropriate period of time)

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to AZD6244 or its excipient Captisol®

- No refractory nausea and vomiting or chronic gastrointestinal diseases (e.g.,
inflammatory bowel disease) that would preclude adequate absorption

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements

- No active illicit substance or alcohol abuse

- Able to understand and willing to sign a written informed consent document

- Recovered from prior therapy

- At least 4 weeks since prior chemo embolization, radio embolization (90Y
microspheres), resection, or radio frequency/cryoablation

- Must have measurable disease outside the treated area or unequivocal evidence of
disease progression within the treated area

- More than 4 weeks since prior radio therapy or major surgery

- No prior organ transplantation

- No prior systemic chemotherapy

- No prior sorafenib

- No prior therapeutic antibody or experimental systemic therapy (oral or intravenous)

- No prior hepatic artery infusion of chemotherapy

- No prior mitogen-activated protein kinase inhibitor

- No prior significant bowel resection that would preclude adequate absorption

- No concurrent fruit or juice of the grapefruit during AZD6244 therapy

- No concurrent anti retroviral therapy for HIV-positive patients

- No other concurrent investigational or commercial agents or therapies for this cancer