Hypoxia regions, which have been demonstrated to widely exist in various solid tumors, are associated with remote metastasis, bad prognosis and resistance to radiation and chemotherapy. Hypoxia-inducible factor-1(HIF-1) plays a crucial role in the hypoxia signaling pathway. It not only increases the viability of tumor cells under the hypoxia condition, but also stimulates angiogenesis and malignant transformation. Therefore, HIF-1 is regarded as a very attractive target in cancer treat- ment. The regulating pathways of HIF-1 are extremely complex, including oxygen concentration, glucose metabolism, mutations in proto-oncogenes and cancer suppressor genes, the PI3K-MAPK -mTOR signaling pathway, free radicals, antioxidants, etc. The regulation of oxygen concentration has been well studied, while the regulations of free radicals, DNA mutation and glucose metabolism are the current hot spots. This paper reviews the elaborate progress in the regulation of HIF-1 activity, which is expected to be helpful to research on anti-tumor drugs targeting HIF-1.