Moreover, we report that high OPN expression in HCC tumor tissues is significantly associated with expression of HIF-1α and that OPN binds to integrin αvβ3 and initiates a signaling cascade that results in upregulation of HIF-1α expression via activation of the transcription factor NF-kB, resulting in an increase of tumorigenic capacity of HCC cells. This evidence concerns the gene HIF1A and hepatocellular carcinoma.