Iron homeostasis consists in providing iron for a variety of biochemical processes and in limiting iron availability for Fenton reaction. Intracellular and systemic iron homeostasis is an important element in the defense against oxidative stress and is controlled by post-transcriptional regulatory mechanism IRP/IRE and hepcidin, a peptide that regulates iron absorption from diet and heme iron release by macrophages. Mutations in hepcidin gene as well as in genes involved in hepcidin regulation lead to the toxic accumulation of iron in the body and exacerbate oxidative stress. Reactive oxygen species influence labile iron pool through the transcriptional and posttranscriptional regulation of ferritin gene and through the release of iron from iron-sulfur proteins and from ferritin degraded in lysosomes. Alcohol-induced oxidative stress down-regulates hepcidin expression, increases iron absorption and leads to the excessive accumulation of iron and oxidative damage in the liver.