OBJECTIVES: Although hepatocellular carcinoma (HCC) is a highly prevalent disease in East Asia with a growing incidence in the US, there is a limited understanding of healthcare procedures and their economic impact.  This study identifies the procedures with the highest payer budget impact in a commercially insured US population. METHODS: The MEDSTAT insurance claims database (January 1, 2000 – December 31, 2008) was used to identify a cohort of patients with >=1 HCC claim (index=1st claim), age >= 18, and no other cancer diagnoses.  For each procedure code, all payments (2009 USD) were summed across the cohort and divided by the total patient-months to estimate the per patient-month (PM) cost.  The PM costs were ranked to identify procedures with the highest payer budget impact.  The proportion of patients utilizing each procedure was calculated to evaluate whether PM costs were driven by a minority of patients.  RESULTS: The study sample included 2927 patients: mean age 50.4 years, 57% male, and median 9 months follow-up. The inpatient procedures with the highest budget impact were:  liver transplant and/or intestinal transplant ($526/PM, 4.6% of patients), tracheostomy with mechanical ventilation ($204/PM, 0.2%), disorders of liver except malignancy/cirrhosis/alcoholic hepatitis ($96/PM, 5.1%).  For hospital outpatient procedures, they were:  magnetic resonance imaging (MRI) of the abdomen ($18/PM, 15%), computed tomography of abdomen ($13/PM, 17%), and transcatheter occlusion/embolization ($8/PM, 4%). For office outpatient procedures, they were:  low complexity visits ($26/PM, 70%), moderate complexity visits ($18/PM, 18%), and MRI of abdomen ($8/PM, 7%).  Patients with >=1 sorafenib prescription (<2% of cohort) had a minimal impact on the results. CONCLUSIONS: The key procedures with the highest budget impact appear to be related to both cancer and liver disease. These costs may be reduced with improved anti-cancer therapy which provides better cancer control and reduces the exacerbation of liver disease from tumor growth.