Primary squamous cell carcinoma (SCC) of the liver is rare and has an extremely poor prognosis. It is very difficult to detect and is sometimes misdiagnosed. It has been reported that male sex, hepatic cyst, hepatolithiasis, hepatic teratoma, and liver cirrhosis may be associated with SCC of the liver. A 67-year-old woman was admitted to our hospital with anorexia, weakness, and right upper quadrant abdominal (RUQ) pain. Sonography and an abdominal computed tomography scan revealed a 36 × 34 cm mass in the liver. Pathological analysis of the sample suggested SCC. According to the negative radiographic findings in other major organs, the tumor was considered primary. The patient was treated with surgical resection and followed by palliative care. Our case died 5 months after the initial presentation.