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Iron\u2010containing proteins play critical roles in cellular functions. The biological importance of iron is largely attributable to its chemical properties as a transitional metal. However, an excess of \u2018free\u2019 reactive iron damages the macromolecular components of cells and cellular DNA through the production of harmful free radicals. On the contrary, most of the body\u2019s excess iron is stored in the liver. Not only hereditary haemochromatosis but also some liver diseases with mild\u2010to\u2010moderate hepatic iron accumulation, such as chronic hepatitis C, alcoholic liver disease and nonalcoholic steatohepatitis, are associated with a high risk for liver cancer development. These findings have attracted attention to the causative and promotive roles of iron in the development of liver cancer. In the last decade, accumulating evidence regarding molecules regulating iron metabolism or iron\u2010related cell death programmes such as ferroptosis has shed light on the relationship between hepatic iron accumulation and hepatocarcinogenesis. In this review, we briefly present the current molecular understanding of iron regulation in the liver. Next, we describe the mechanisms underlying dysregulated iron metabolism depending on the aetiology of liver diseases. Finally, we discuss the causative and promotive roles of iron in cancer development.<\/jats:p>","DOI":"10.1111\/febs.16208","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T13:06:57Z","timestamp":1632143217000},"page":"7810-7829","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Iron and liver cancer: an inseparable connection"],"prefix":"10.1111","volume":"289","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3297-1720","authenticated-orcid":false,"given":"Keisuke","family":"Hino","sequence":"first","affiliation":[{"name":"Department of Hepatology and Pancreatology Kawasaki Medical School  Kurashiki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Yanatori","sequence":"additional","affiliation":[{"name":"Department of Pathology and Biological Responses Nagoya University Graduate School of Medicine  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