Abstract: Objective To study the serum IL-34 level of neonatal hypoxic-ischemic encephalopathy(HIE) and explore its clinical significance in HIE. Methods Eighty children with HIE were selected as the HIE group and 80 healthy newborns were selected as the control group from January 2017 to December 2019 in Ningbo Women's and Children's Hospital. The serum IL-34, IL-17 and IL-23 levels were measured using double-antibody sandwich enzyme-linked immunosorbent assay. NABA scores were used to assess the severity of brain damage. Results The serum levels of IL-34 [(24.36±2.41)ng/L], IL-17[(118.79±9.76)ng/L] and IL-23[(63.24±3.46)ng/L] in the HIE group were higher than those in the control group[(13.25±2.02)ng/L,(47.53±8.02)ng/L,(15.42±3.12)ng/L], all P<0.05, and the NABA score[(30.25±2.02)scores] was lower than that in the control group [(37.86±1.74)scores],P<0.05. There were significant differences in serum levels of IL-34, IL-17, IL-23 and NABA scores in children with different severity of HIE(all P<0.05): with the increase of severity of HIE, serum IL-34, IL-17 and IL-23 levels increased, and NABA score decreased. There were significant differences in serum IL-34, IL-17 and IL-23 levels in children with different NABA scores(all P<0.05): with the abnormal degree of NABA score increasing, serum IL-34, IL-17, IL-23 levels decreased. The level of serum IL-34 in children with HIE was positively correlated with the levels of IL-17 and IL-23(all P<0.05). NIE scores in children with HIE were negatively correlated with serum IL-34, IL-17 and IL-23 levels(all P<0.05). Conclusion The serum IL-34 level of HIE neonates is increased, and IL-34 may participate in the brain damage process of children through interaction with Th17-related cytokines.