Purpose We aimed to investigate the recommended dose for the combination of TSU-68, a multiple-receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2 and platelet-derived growth factor receptor-β, and S-1, an oral fluoropyrimidine, in patients with advanced hepatocellular carcinoma (HCC) based on its associated dose-limiting toxicity (DLT) frequency. This evidence concerns the gene PSMD1 and hepatocellular carcinoma.