Brain injury of premature infant can be secondary to a variety of serious complications, with the increase of premature birth rate. The severe neurological sequelae has become a new clinical, public health and social problems. It has been found that erythropoietin (EPO) can reduce premature brain damage, protect and repair damaged nerve cells, and improve the long-term prognosis of nervous system. The main mechanism of EPO neuroprotective effect is to promote cerebrovascular maturity, relieve vasospasm, promote angiogenesis and establish collateral circulation to improve cerebral ischemia damage. Other neuroprotective mechanisms include anti-apoptosis, anti-inflammatory and so on. In addition, EPO can also increase proliferation of neurons and enhance neural function. EPO may provide a new approach for promoting survival and growth in nerve cells and hold great promise for the future treatments of premature brain injury.