Advanced hepatocellular carcinoma (HCC) with distant metastases, in particular to the lung, has a poor prognosis. This study was undertaken to evaluate the effectiveness of TS-1 as chemotherapy in advanced HCC with lung metastases. Between January 2004 and October 2005, 8 patients with advanced HCC with lung metastasis were enrolled. All patients received systemic chemotherapy with TS-1. The drug was administered at a dose of 80 mg/m(2)/day for four weeks, followed by a two-week rest, repeated every six weeks until disease progression, unacceptable toxicity, or the patient's refusal. Median age of the patients was 59 years (range, 44 to 79 years). All patients were in Child-Pugh class A. A total of 22 cycles were administered to each patient (range, 1 to 5). No complete or partial responses were observed. There were two patients (25%) with decreasing tumor marker. Median progression-free survival was 79.5 days (range, 29 to 225). The median overall survival was 257 days (95% confidence interval, 191 to 323 days). TS-1 as chemotherapy was well tolerated when administered in the schedule used in this study. Some patients achieved stable disease and clinical benefits, though this regimen has limited activity in HCC with lung metastases. Randomized controlled trials are necessary to clarify survival benefits in patients with advanced HCC with lung metastasis.