Transarterial radioembolization (TARE) with ¹⁶⁶Ho-loaded microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), introduced in 2010. This study evaluates the clinical outcome of patients with HCC who underwent ¹⁶⁶Ho-TARE with personalized dosimetry. Twenty-seven patients with 36 TARE procedures were analyzed. Treatment planning, execution, and evaluation was possible without complications in all cases. At the 3-month follow-up, disease control in the treated liver was achieved in 81.8% of patients (complete remission, partial remission, and stable disease in 36.4%, 31.8%, and 13.6%, respectively). The median overall survival (OS) was 17.2 months, and progression-free survival (PFS) in the treated liver was 11 months. Statistically significant positive correlations were observed between the achieved radiation dose for the tumor and both PFS (r = 0.62, p < 0.05) and OS (r = 0.48, p < 0.05), suggesting a direct dose–response relationship. The calculated achieved dose was 8.25 Gy lower than the planned dose, with relevant variance between planned and achieved doses in individual cases. These results confirm the efficacy of the ¹⁶⁶Ho-TARE holmium platform and underscore the potential of voxel-based, personalized dosimetry to improve clinical outcomes.