The hypoxia-inducible factor (HIF) is a heterodimeric transcription factor that it composed of an oxygen-sensitive α subunit and a constitutively expressed β subunit, which plays crucial role in the cellular response to the stress of hypoxia. HIF prolyl hydroxylase domain-containing proteins (PHDs) and asparaginyl hydroxylase(namely factor-inhibiting HIF, FIH) are critical enzymes that regulate amount of HIF and transcriptional activity of HIF. However, the catalytic activity of these enzymes is governed by the oxygen tension within the cell, which defines these proteins as cell oxygen sensors. To date, most of researches focus on PHDs, while researches about FIH are relatively scarce.This review aims to summarize current researches in FIH, including its discovery,crystal structure, biological features,and the regulation of its expression and activity.