<b><i>Introduction:</i></b> Selective internal radiation therapy (SIRT) is a local treatment option for patients with hepatocellular carcinoma (HCC). Its exact role next to other HCC therapies has yet to be defined. In order to identify patients most suitable for SIRT, a SIRT-specific prognostic score should be developed. <b><i>Methods:</i></b> A cohort of 72 SIRT patients treated at the University Hospital of Munich was retrospectively analyzed. The prognostic performance of 12 HCC staging systems and prognostic scores was assessed. Cox-regression analysis was used to identify independent prognostic factors, which formed the basis of the Munich-SIRT score (M-SIRT). All scores were ranked by calculating the c-Index and Akaike information criterion (AIC). External validation was performed in a cohort of 128 SIRT patients treated at the University Hospital of Pamplona, Spain. <b><i>Results:</i></b> median overall survival was 13 months (95% confidence interval 9.9–21.9). AFP (<i>p</i> = 0.005; hazard ratio [HR] 2.38), albumin (<i>p</i> &#x3c; 0.001; HR 5.87), and alkaline phosphatase (<i>p</i> &#x3c; 0.001; HR 8.38) were identified as independent prognostic factors. M-SIRT comprises 3 prognostic groups with a median survival of 38.9, 14.6, and 7.7 months, respectively (I vs. II: <i>p</i> = 0.003, II vs. III: <i>p</i> &#x3c; 0.001). AIC (318) and concordance index (0.711) ranked M-SIRT superior to the established HCC staging systems, and the score successfully passed external validation in an independent SIRT cohort (I vs. II: <i>p</i> = 0.03; II vs. III: <i>p</i> = 0.007). <b><i>Conclusion:</i></b> Therapy-specific prognostic scores can facilitate treatment decisions and prognostication for HCC patients. Considering its performance in 200 SIRT patients, M-SIRT is a promising prognostic tool for HCC patients evaluated for SIRT.