(1) Background: To demonstrate correlation between skeletal muscle depletion measured before and after one month of TARE treatment and its induced local response rate. (2) Material and methods: For this retrospective, single center study, we evaluated 86 patients with HCC treated with TARE. Sarcopenia status was measured using the psoas muscle index (PMI). The PMI was calculated according to the formula: PMI [mm/m2]: [(minor diameter of left psoas + major diameter of left psoas + minor diameter

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... of right psoas + major diameter of right psoas)/4]/height in m2. Population was divided in two groups according to the delta value of PMI measured at the time of TARE and one month after TARE, a group in which the delta PMI was stable or increased (No-Sarcopenia group; n = 42) vs. a group in which the delta-PMI decreased (Sarcopenia group; n = 44). Patient response was evaluated at 1, 3 and 6 months after TARE treatment with CT/MRI. (3) Results: When the radiological response of the tumor was evaluated according to the mRECIST criteria, the two groups were similar in terms of rates of complete response (p = 0.42), partial response (p = 0.26) and stable disease (p = 0.59). Progressive disease (PD) was more commonly observed in the Sarcopenia group (38.6% vs. 11.9%; p = 0.006). (4) Conclusions: Worsening of sarcopenia status measured one month after TARE is able to predict patients who will undergo disease progression.