Sarcopenia is associated with adverse outcomes in several gastrointestinal malignancies and liver cirrhosis. We aimed to study the utility of magnetic resonance imaging (MRI) derived fat-free muscle area (FFMA) to predict clinical outcome in patients receiving yttrium-90 radioembolization (RE) for treatment of hepatocellular carcinoma (HCC).Fifty-eight patients with unresectable HCC and pre-interventional liver MRI undergoing salvage RE were retrospectively evaluated. Using axial T2-weighted turbo spin echo sequences, FFMA was calculated by subtraction of the intramuscular adipose tissue area from the total cross-sectional area of paraspinal skeletal muscles at the superior mesenteric artery level. FFMA values lower than 3582 mm2 in male and 2301 mm2 in female patients were defined as low FFMA. Main outcomes were progression-free survival (PFS) and overall survival (OS). For outcome analysis, the Kaplan-Meier method with log rank test and multivariate cox regression analysis were used.Mean time from pre-interventional MRI to RE was 27 ± 20 days. Median OS and PFS after RE were 250 (range: 21-1230 days) and 156 days (range: 21-674 days), respectively. Patients with low FFMA showed significantly reduced OS (197 vs. 294 days, P = 0.024) and tended to have shortened PFS (109 vs. 185 days, P = 0.068). Low FFMA (HR 2.675; P = 0.011), estimated liver tumor burden (HR 4.058; P = 0.001), and Eastern Cooperative Oncology Group (ECOG) performance status (1.763; P = 0.009) were independent predictors of OS on multivariate analysis.FFMA as a measure of sarcopenia predicts OS and might represent a promising new biomarker for survival prognosis in patients undergoing RE for treatment of unresectable HCC.