Abstract:〔Abstract〕 Objective To investigate the relationship between serum erythropoietin (EPO), neuron specific enolase (NSE), S100 calciu binding protein B (S100B), myelin basic protein (MBP) and hemorrhagic brain injury in premature infants. Methods Preterm infants aged 28 to 34 weeks admitted to the Second People's Hospital of Shenzhen, Shenzhen Maternal and Child Health Hospital, Shenzhen People's Hospital and Shenzhen Longhua District People's Hospital from October 2014 to September 2015 were prospectively selected as subjects. According to the results of head ultrasound and head magnetic resonance imaging (MRI), they were divided into hemorrhagic brain injury group and nonbrain injury group. Serum concentrations of EPO, NSE, S100B and MBP were determined by enzyme-related immunosorbent assay (ELISA). The levels of serum EPO, NSE, S100B protein and MBP were compared between the two groups, and the relationship between the levels and hemorrhagic brain injury of premature infants was analyzed. Results The level of serum EPO in hemorrhagic brain injury group was lower than that in no brain injury group, and the levels serum NSE, S100B and MBP were higher than those in no brain injury group, the differences were statistically significant (P < 0.05). Systolic blood pressure and platelet count in hemorrhagic brain injury group were lower than those in no brain injury group, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that high concentrations of serum EPO, systolic blood pressure, and platelet count are protective factors for hemorrhagic brain injury, while high concentrations of NSE and S100B protein and male children are risk factors for hemorrhagic brain injury. Conclusion The levels of serum EPO, NSE, S100B and MBP are closely related to hemorrhagic brain injury in premature infants. At the same time, it is necessary to strengthen the monitoring of platelet count and blood pressure management in male premature infants in clinical practice.