Abstract: 【Abstract】 Objective To investigate the relationship between neonatal bronchopulmonary dysplasia (BPD) and serum interleukin-1 receptor-associated kinase 4 (IRAK4) and transcription factor forkhead box O3a (FOXO3a) expression levels. Method A total of 260 neonates born and hospitalized in the Department of Neonatology, Hainan General Hospital from March 2019 to May 2022 were collected as the study subjects. The neonates with BPD were included into the study group (n=99) and neonates without BPD were included in the control group (n=161). The expression levels of serum IRAK4 and FOXO3a of the two groups were detected by enzyme-linked immunosorbent assay, and the relationship between clinicopathological characteristics of BPD and serum IRAK4 and FOXO3a levels was analyzed. The predictive value of serum IRAK4 and FOXO3a levels for BPD was analyzed by receiver operating characteristic (ROC) curve. Statistical methods included t-test, ANOVA, χ2 test and Pearson correlation analysis. Result The expression level of IRAK4 in the study group was higher than that in the control group [(1.07±0.33) vs (0.65±0.18) ng/L, t=13.265, P<0.001], and the expression level of FOXO3a was lower than that in the control group [(0.53±0.15) vs (0.83±0.24) g/L, t=11.164, P<0.001]. Pearson correlation analysis results showed that there was a negative correlation between the expression level of serum IRAK4 and FOXO3a in neonates with BPD (r=-0.582, P<0.001). The expression level of serum IRAK4 and FOXO3a in neonates with BPD were not related to their gender and delivery style (all P>0.05); but they were related to gestational age, body mass, and severity of the disease (all P<0.05). The expression level of IRAK4 increased with the decrease of fetal age, body mass, and severity of the disease, while theexpression level of FOXO3a decreased with the decrease of fetal age, body mass, and severity of the disease.The area under the curve (AUC) of serum IRAK4 and FOXO3a expression level in predicting BPD was 0.813(95%CI: 0.754-0.873) and 0.791 (95%CI: 0.728-0.855), respectively; the AUC of combined prediction ofIRAK4 and FOXO3a for BPD was 0.910 (95%CI: 0.870-0.949). Conclusion Neonates with BPD havehigh expression of serum IRAK4 and low expression of serum FOXO3a, and the combined detection has ahigh diagnostic value for the occurrence of neonatal BPD.