Background: Sarcopenia is associated with overall survival in patients with hepatocellular carcinoma (HCC). However, it is not known whether muscle volume is associated with clinical outcomes during combination therapy with immune checkpoint inhibitors. We investigated the relationship between changes in muscle volume and treatment outcomes in patients treated with atezolizumab plus bevacizumab. Methods: Thirty-two patients with HCC who received atezolizumab plus bevacizumab as the first-line treatment between October 2020 and February 2022 were included. Skeletal muscle mass index (SMI) was calculated from the skeletal muscle area at the L3 level of the lumbar vertebrae. We compared pretreatment SMI and SMI at 6–14 weeks after administration. Results: Of the 32 patients, 18 had a decreased SMI, while 14 did not. Progression-free survival (PFS) was significantly longer in patients without SMI decrease than in patients with SMI decrease (8.5 vs. 5.8 months, p = 0.011). There were no significant differences in treatment-related adverse events between the patients with and without SMI. Presarcopenia at baseline was not significantly associated with PFS. Conclusions: Decreased SMI was significantly associated with PFS. Monitoring muscle volume during atezolizumab plus bevacizumab therapy is useful in clinical practice.