Inclusion Criteria:

- Patients must have microscopically confirmed hepatocellular carcinoma not amenable to
curative resection; if patients have an isolated lesion in one lobe of the liver, a
liver surgeon should determine resectability; central review is not required

- Patients must have measurable disease as determined by RECIST criteria, amenable to
biopsy; patients are not mandated to allow biopsy, even though it is an important
aspect of this clinical trial

- Patients with history of untreated malignancy other than HCC are not eligible

- Patients with history of malignancy treated within the past 5 years are not eligible;
history of carcinoma-in-situ of cervix, squamous cell cancer of skin, basal cell
cancer of skin, previously treated are allowed; others are excluded as recurrence of
disease may confuse response rate and/or survival endpoints

- Patients must have ECOG performance status of 0-2

- Patients must not have had prior systemic chemotherapy for HCC; patients on
antineoplastics for non-malignant diseases, such as methotrexate for rheumatoid
arthritis, are allowed, providing patients have been off these agents for at least 4
weeks and all related toxicities have resolved to baseline

- Patients must not have had prior use of octreotide or tamoxifen as therapy for HCC

- Patients may have had prior embolization without chemotherapy; patients who have had
chemoembolization are not eligible; patients may have had radiofrequency (RF)
ablation, cryosurgery or ethanol injection; patients must have documented progression
with the involved lesion or at least one previously untreated lesion amenable to
biopsy

- Platelet count must be >= 100,000/mm^3 in absence of splenomegaly; platelet count
must be >= 75,000/mm^3 with splenomegaly

- ANC must be >= 1,500/mm^3 in absence of splenomegaly; ANC must be =< 1,000/mm^3 with
splenomegaly

- Alkaline phosphate must be =< 5 x institutional ULN

- AST must be =< 5 x institutional ULN

- Bilirubin must be =< 2 mg/dl

- Patients may not exhibit Child Pugh scale grade C cirrhosis

- Serum creatinine=< 2.0 mg/dl

- Patients must have no baseline peripheral neuropathy > grade 1

- Patients with known allergy to boron, mannitol or bortezomib are not eligible

- Women must not be pregnant or breast-feeding due to the uncertain effects of
bortezomib in the developing fetus and young infants

- All females of childbearing potential must have a blood test or urine study within 2
weeks prior to registration to rule out pregnancy

- Women of childbearing potential and sexually active males are strongly advised to use
an accepted and effective method of contraception

- Patients must not have an underlying medical condition that precludes safe
participation in this clinical trial

- Patients must not have psychiatric illness or continued substance abuse that may
impair the ability to provide informed consent or prevent safe administration of
bortezomib

- Patients must not have known bleeding diathesis, INR > 1.5 or PTT > 1.5 x
institutional ULN (required due to biopsy portion of study); use of vitamin K or
fresh frozen plasma to correct values just prior to biopsy or enrollment is not
allowed

- Patients with EF < 50% measured by ECHO or MUGA are not eligible

- Patients on verapamil who cannot be switched to an alternative medication are not
eligible (due to the interaction with doxorubicin)