OBJECTIVES:  Sorafenib has demonstrated improved overall survival in patients with hepatocellular carcinoma (HCC). Many patients (80%) taking sorafenib experience adverse events (AEs) leading to dose reductions (26%) and drug discontinuation (38%). The objective of this retrospective analysis is to describe patients in the US with HCC who cease sorafenib treatment after one prescription. METHODS:  The study cohort was US patients with two separate diagnoses of HCC receiving first line (1L) treatment with one or more sorafenib pharmacy claims between July 1, 2007 and September 30, 2015 in the Truven Marketscan® Commercial and Medicare supplemental claims databases. Descriptive statistics characterized patient baseline demographics, clinical characteristics, sorafenib treatment-related variables, and AEs. RESULTS: Among 1,861 patients in the study cohort, 704 (38%) patients received only one sorafenib claim. Of the 704 patients, the mean age was 63.5 years (SD=10.74), and 78.8% were male. Non-alcoholic liver disease, cirrhosis, and hepatitis C were the most common (>25%) hepatic-related comorbidities. The mean prescribed average daily dose of sorafenib was 713.3mg/day (SD=179.45) (89% of the labeled dose) among patients with complete prescription claims (97.4%). The median time from diagnosis to sorafenib initiation was 35 days. Nausea/vomiting, anorexia/weight loss, fatigue, and musculoskeletal/joint pain were the most common AEs (>5%) during sorafenib treatment. Most patients (93.3%) did not receive subsequent therapy with an alternative anti-cancer agent, however, for those who did the median time to initiation of subsequent therapy was 49 (Range: 1-456) days after sorafenib initiation. CONCLUSIONS:  Over one-third of patients with HCC in the US fill only one sorafenib 1L prescription, and most do not receive subsequent drug therapy, demonstrating unmet medical need. Some patients receive less than the labeled dose. Factors associated with dose reduction and discontinuation and the impact on real-world effectiveness of first line sorafenib should be investigated.