Oxygen is a mandatory for all aerobic organisms. Oxygen-containing free radicals are produced when oxygen is not completely reduced to water in energy-producing oxidation reaction. The radicals may also transform into other reactive compounds through electron transfer and all the compounds with similar functions are referred as reactive oxygen species （ROS）. Increased ROS is known to cause damage to proteins, DNA and lipids. Much evidence showed that changes in partial oxygen pressure, hormone, cytokine and chemical stimulation could increase ROS, and ROS, acting as signaling molecules, mediates cell functions. Hypoxia-inducing factor （HIF）, a key transcriptional factor for most hypoxia-inducible genes, is a heterodimer consisting of 2 subunits. Recent study found that ROS plays an important role in HIF activity regulation under hypoxic and non-hypoxic conditions. This paper reviews the production of ROS and its role in the regulation of HIF activity