Mutations in polycystin-1 which is encoded by thePKD1gene are the main causes for the development of autosomal dominant polycystic kidney disease. However, only little is known about the physiological function of polycystin-1 and even less about the regulation of its expression. Here, we show that expression ofPKD1is induced by hypoxia and compounds that stabilize the hypoxia-inducible transcription factor (HIF) 1αin primary human tubular epithelial cells. Knockdown of HIF subunits confirms HIF-1α-dependent regulation of polycystin-1 expression. Furthermore, HIF ChIP-seq reveals that HIF interacts with a regulatory DNA element within thePKD1gene in renal tubule-derived cells. HIF-dependent expression of polycystin-1 can also be demonstratedin vivoin kidneys of mice treated with substances that stabilize HIF. Polycystin-1 and HIF-1αhave been shown to promote epithelial branching during kidney development. In line with these findings, we show that expression of polycystin-1 within mouse embryonic ureteric bud branches is regulated by HIF. Our finding links expression of one of the main regulators of accurate renal development with the hypoxia signalling pathway and provides additional insight into the pathophysiology of polycystic kidney disease.