Abstract: Iron overload refers to a condition resulting in increased body iron stores, with or without organ dysfunction. Among the secondary iron overload syndromes, besides blood transfusion dependency, a group of anemias that arise from ineffective erythropoiesis may manifest a feature of iron overload. A group of candidate molecules such as hepcidin are identified to serve as vital “singles” in the process. With the up-to-date research achievements of this field, this review mainly states the mechanism and the latest development that how ineffective erythropoiesis cause tissue iron overload.