Development of a curative local treatment for large hepatocellular carcinoma (HCC) is an important issue. Here, we investigated the dose homogeneity, safety and antitumor effectiveness of proton beam therapy (PBT) using a patch-field technique for large HCC. Data from nine patients (aged 52-79 years) with large HCC treated with patch-field PBT were investigated. The cranial-caudal diameters of the clinical target volumes (CTVs) were 15.0-18.6 cm (median 15.9). The CTV was divided cranially and caudally while both isocenters were aligned along the cranial-caudal axis and overlap of the cranial and caudal irradiation fields was set at 0-0.5 mm. Multileaf collimators were used to eliminate hot or cold spots. Total irradiation doses were 60-76.4 Gy equivalents. Irradiation doses as a percentage of the prescription dose (from the treatment planning system) around the junction were a minimum of 93-105%, a mean of 99-112%, and a maximum of 105-120%. Quality assurance (QA) was assessed in the cranial and caudal irradiation fields using imaging plates. Acute adverse effects of Grade 3 were observed in one patient (hypoalbuminemia), and a late adverse effect of Grade 3 was observed in one patient (liver abscess). Child-Pugh class elevations were observed in four patients (A to B: 3; B to C: 1). Overall survival rates at 1 and 2 years were 55 and 14%, respectively, with a median overall survival of 13.6 months. No patients showed local recurrence. Patch-field PBT supported by substantial QA therefore is one of the treatment options for large HCC.