Hypoxia-inducible factor-1alpha (HIF-1alpha), a nuclear transcriptional factor, is constitutively expressed in mammalian cells under hypoxia, which contributes a lot to the regulation of internal O2 homeostasis. Micro-environmental hypoxia is a common feature of solid tumors. Under the stress of hypoxia, HIF-1alpha is accumulated and activated, which leads to activation of a vast array of downstream genes that contribute to tumor O2 homeostasis and energy metabolic equilibrium. HIF-1alpha weighs heavily in favor of tumor genesis and progression. So far, HIF-1alpha has became an attracting tumor research topic, which improves understanding on how HIF-1alpha functions in tumor progression and key signaling pathways that regulate HIF-1alpha, therefore, provides new scientific supports and ideas to look for novel target for tumor therapy.