This study further linked HIF-1α, Piezo1 and pro-angiogenic factors, elucidating that high stiffness-induced Piezo1 activation significantly upregulates HIF-1α and its downstream targets, including VEGF, IGFBP2 and CXCL16, thereby promoting HCC angiogenesis. This evidence concerns the gene PIEZO1 and hepatocellular carcinoma.