This case report describes a 12-year-old female spayed mixed-breed dog referred for treatment of a large, inoperable hepatocellular carcinoma. A computed tomography (CT) scan confirmed the previous ultrasonographic and laparoscopic findings of a large, lobulated, poorly defined mass on the left and central aspect of the liver. Multiple biopsies confirmed the diagnosis of hepatocellular carcinoma. Due to the large extent of the tumor, the vascular association to the Vena cava caudalis and the associated high risk of intraoperative bleeding, a resection of the mass was refrained from and a radiotherapeutic treatment was chosen. The dog underwent radiation therapy (RT) with a 6MV linear accelerator with 5×6 Gy, total dose 30 Gy. In the follow up examinations three months and one year after therapy, the dog presented in normal condition and had normal Alanine-aminotransferase (ALT) and alkaline phosphatase (AP). The tumor size measured in the CT-examinations decreased by 61% and 90%, respectively. Two years after radiation therapy the dog has a normal general condition and liver enzymes are within the normal limits.