Background: Trans-arterial radioembolization (TARE) is a form of radiation therapy performed by selective intra-arterial injection of microspheres loaded with Yttrium-90 in hepatocellular carcinoma (HCC). The aim of this study is to identify prognostic factors for overall survival (OS) and progression free survival (PFS) in patients with HCC undergoing TARE. Methods: This is a multi-center retrospective study on consecutive HCC patients undergoing TARE from Jul 2009 to May 2019. Using pre-treatment plain computed tomography imaging, the total cross-sectional area (cm2) of abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing muscle area to patient height. Results: A total of 347 patients were included in the study (mean age 66 years, 284 male patients). 107 patients (30.8%) had portal vein tumor thrombus (PVTT). 126 patients (36.3%) were classified as sarcopenia. Median 5-year OS was 31.3 months (95% CI 24.7–37.9) and median 12-month PFS was 9.7 months (95% CI 8.0–11.4). Sarcopenia (HR, 1.44; 95% CI, 1.01-2.04, p=0.04), PVTT (HR, 1.70; 95% CI, 1.13-2.56, p=0.01), hypoalbuminemia (≤3.5 g/dL) (HR 1.64; 95% CI 1.17-2.30, p<0.01), and prior treatment experience (HR 1.61; 95% CI 1.00-2.57, p=005) were independently associated with poor 5-year OS by multivariate Cox regression analysis. Sarcopenia, PVTT, multifocal tumor, and prior treatment experience were independent predictors of PFS in multivariate analysis. Conclusions: TARE is an effective therapy for patients with advanced HCC. In patients undergoing TARE, Sarcopenia and PVTT are independent predictors of both OS and PFS.