OBJECTIVES: Hepatocellular carcinoma (HCC) is a rapidly progressing, fatal disease.  However, little is known regarding the hospitalization burden for these patients.  This study compares the burden of hospitalizations due to HCC and hepatobiliary conditions relative to other non-hepatobiliary comorbid conditions. METHODS: Insurance claims (Janaury 1, 2000-December 31, 2008) from a geographically diverse, commercially insured US population were used to identify a cohort of patients with >=1 HCC claim (index=1st claim), age>=18, and no other cancer diagnoses in the year prior to index.  Hospitalizations were grouped by primary diagnosis (ICD-9) codes into the following categories: 1) HCC and hepatobiliary, and 2) non-hepatobiliary.  Hospitalization burden was compared between these categories based on: number of hospitalizations, time to occurrence since HCC diagnosis, length of stay, and cost (2009 USD).  The number of hospitalizations was compared using a sign test for patient-level differences.  The remaining parameters were compared using general estimating equations to adjust for patients with multiple hospitalizations. RESULTS: This study identified 2927 HCC patients (mean age 50.4 years, 57% male) and 2192 hospitalizations.  The subset of patients with >=1 hospitalization (n=1083, 37%) had an average of 2.02 admissions per patient with a median of 11.8 follow-up months.  Compared to the non-hepatobiliary hospitalizations, the HCC and hepatobiliary hospitalizations had: a higher number of admissions (0.40 vs. 0.35 per patient; p<0.001), a shorter time to occurrence (112 vs. 330 days; p<0.001), a longer length of stay (6.4 vs. 5.4 days; p<0.007), and a higher average cost per admission ($48,539 vs. 23,221; p<0.001).  The total cost of HCC and hepatobiliary hospitalizations was 2.3 times higher than non-hepatobiliary hospitalizations ($56,451,173 vs. $23,894,444). CONCLUSIONS: HCC and hepatobiliary conditions accounted for the majority of the hospitalization burden in liver cancer patients.  Future HCC therapies demonstrating reduced symptom progression may reduce the prevalence, duration, and cost of HCC and hepatobiliary-related hospitalizations.