Simple SummaryProton beam therapy (PBT) has not been generally recommended as an initial treatment for hepatocellular carcinoma (HCC) due to the insufficiency of data on PBT for treatment-naïve HCC until now, and albumin-bilirubin (ALBI) grade has been shown to be an effective assessment of liver dysfunction and more discriminatory for survival than the Child–Pugh classification. This study evaluated the efficacy of PBT as first-line treatment in treatment-naïve HCC and assessed the prognostic significance of ALBI grade in these patients. Our findings showed that PBT could result in comparable local tumor control and survival outcomes in treatment-naïve HCC patients to those of other recommended first-line treatments, with a safe toxicity profile compared to our institutional cohort data and previous other studies, and ALBI grade and tumor stage were independent predicting factors for overall survival.To evaluate the efficacy of proton beam therapy (PBT) as an initial treatment in treatment-naïve hepatocellular carcinoma (HCC) patients and to assess the prognostic significance of albumin-bilirubin (ALBI) grade, 46 treatment-naïve HCC patients treated with PBT were analyzed. The ALBI grade distribution was grade 1 in 11 (23.9%) patients, grade 2 in 34 (73.9%) patients, and grade 3 in 1 (2.2%) patient. The median duration of follow-up was 56.5 months (95% confidence interval [CI], 48.2–64.7). Among the 46 patients, disease progression was observed in 23 (50%) patients: local progression in 3 (6.5%) patients; intrahepatic progression in 22 (47.8%); and extrahepatic progression in 5 (10.9%). The 5-year freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were 92.7% (95% CI, 84.7–100.7), 43.3% (95% CI, 28.2–58.4), and 69.2% (95% CI, 54.9–83.5), respectively. In multivariate analysis, there were no independent factors for FFLP (p > 0.05 each), but tumor stage and ALBI grade were independent factors for PFS and OS (p < 0.05 each). PBT could result in comparable OS in treatment-naïve HCC patients to other recommended first-line treatments, and ALBI grade, in addition to tumor stage, could be useful for predicting OS.