Background: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a major stimulatory factor for choroidal neovascularization. The upregulation of VEGF expression in response to hypoxia occurs through hypoxia-inducible factor 1 (HIF-1), which is a transcription factor that regulates genes involved in the response to hypoxia. HIF-1α is the inducible subunit of the HIF-1. Aims: To further define HIF-1 function in angiogenesis and to explore novel approaches to modulate choroidal neovascularization in age-related macular degeneration. Methods: In this study, we examined the response of human retinal pigment epithelium (RPE) cells to hypoxia and employed the small interference RNA technique to knock down gene expression of HIF-1α in RPE cells. Results: We found that both the mRNA and protein levels of HIF-1α in the RPE cells increased in response to hypoxia, followed by increasing expression of VEGF. Both the mRNA and protein levels of HIF-1α and VEGF in the RPE cells were decreased dramatically after transfection with a HIF-1α-specific small interference RNA vector. Conclusion: Our results suggest that HIF-1 may be involved in angiogenesis by controlling the expression of VEGF in vivo and provide a possible strategy for the treatment of angiogenesis by targeting the HIF-1α in ischemic retinopathies.