Objective To explore the risk factors for brain injury in premature infants.Methods We selected 204 premature infants with gestational age no less than 196 days who were hospitalized in neonatal intensive care unit of The Second Hospital of Dalian Medical University from September 2016 to January 2019, and divided them into brain injury group and non-brain injury group. The demographic data, potentially-relevant factors in the fetal and neonatal period and maternal conditions of the premature infants were compared between the groups.Results The gestational age and birth weight were lower in the brain injury group compared with the non-brain injury group (P < 0.05). There were differences in the presence of maternal diseases including hypertensive disorder complicating pregnancy, gestational diabetes mellitus and infections during pregnancy (P < 0.05). The incidence of preterm premature rupture of membranes lasting longer than 18 hours, abnormality of umbilical cord, and multiple gestation was also different between the groups (P < 0.05). Besides, the premature infants of the two groups differed in the presence of neonatal asphyxia, disseminated intravascular coagulation, infections, and respiratory failure, as well as in the needs for mechanical ventilation and blood transfusion (P < 0.05). In comparison with the non-brain injury group, the levels of hemoglobin and hematocrit were higher, but free thyroxine level was lower in the brain injury group (P < 0.05). Multivariate regression analysis showed that gestational age < 34 weeks [R = 2.561 (95% CI: 1.025, 6.402)], high hemoglobin concentration [R = 1.078 (95% CI: 1.040, 1.118)], neonatal infections [R = 4.047 (95% CI: 1.293, 12.836)], neonatal asphyxia [R = 8.385 (95% CI: 1.282, 54.825)], neonatal disseminated intravascular coagulation [R = 22.005 (95% CI: 2.220, 218.163)], gestational diabetes mellitus [R = 3.102 (95% CI: 1.274, 7.553)], gestational infections [R = 4.401 (95% CI: 1.133, 17.10)] and mechanical ventilation requirement in neonates [R= 6.979 (95% CI: 1.425, 34.173)] were the risk factors for brain injury in premature infants (P < 0.05).Conclusions There are multiple risk factors for brain injury in premature infants, including gestational age less than 34 weeks, high hemoglobin concentration, neonatal infection, neonatal asphyxia, neonatal disseminated intravascular coagulation, needs for mechanical ventilation in neonates, gestational diabetes mellitus and gestational infections, among which neonatal disseminated intravascular coagulation has the greatest impact on brain injury.