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Purpose This study was conducted to evaluate the safety and efficacy of proton beam therapy for large hepatocellular carcinoma (HCC). Methods Twenty-four patients with a HCC larger than 5.0 cm were treated with proton beam therapy at our institution between 2008 and 2015. Results The clinical stage was I in 2 patients, II in 9 patients and IIIB in 13 patients. Ten of the 24 patients were not surgical candidates because of advanced HCC or old age. Median tumor size was 90 mm (range, 50-180 mm). Median total dose delivered was 72.6 Gray-equivalents (GyE) in 22 fractions (range, 60.8-85.8 GyE). Median follow-up period was 17.5 months (range, 3-70 months). Local control rate at 2 years was 87.0%. The 2-year overall survival rate was 52.4%. The predominant tumor progression pattern was new hepatic tumor development outside the irradiated field. No acute or late treatment-related toxicity of Grade 3 or higher other than dermatitis was observed. Conclusions These results demonstrate that proton beam therapy offers an effective and safe method for treating patients with large HCC. Proton beam therapy represents a promising modality for treatment of large-volume HCC.