In this study, we revealed that the conditioned medium from HCC cells, containing S1P, IL-6 and VEGFA, induced the overexpression of S1PR1 and promoted angiogenesis of EC via the activation of STAT3; and stattic could block the increasing level of S1PR1 which was induced by S1P, IL-6 and VEGFA, suggesting static may be a potential drug used in HCC antiangiogenic treatment. This evidence concerns the gene S1PR1 and hepatocellular carcinoma.