A 65-year-old man underwent a total gastrectomy and distal pancreatectomy for acinar cell carcinoma of the pancreas. Multiple metastatic liver lesions were found one year postoperatively. He was treated with S-1 chemotherapy over 34 months, and the tumors significantly reduced in size without severe side effects. Four years after surgery, the liver metastases increased in size, associated with pain especially in the right upper quadrant. We then performed right hepatectomy. Peritoneal dissemination and multiple lung metastases were found 8 months after liver resection. Acinar cell carcinoma of the pancreas is a rare and highly malignant tumor, and there are few reports regarding treatment with chemotherapy. Herein, we report a case with multiple liver metastases which were controlled by systemic chemotherapy using S-1.