Excessive oxidative stress resulting from hyperoxia or hypoxia is a recognized risk factor for diseases of prematurity. However, the role of the hypoxia-related pathway in the development of these diseases has not been well studied. Therefore, this study aimed to investigate the association between four functional single nucleotide polymorphisms (SNPs) in the hypoxia-related pathway, and the development of complications of prematurity in relation to perinatal hypoxia. A total of 334 newborns born before or on the 32nd week of gestation were included in the study. The SNPs studied wereHIF1Ars11549465 and rs11549467,VEGFArs2010963, and rs833061. The findings suggest that theHIF1Ars11549465T allele is an independent protective factor against necrotizing enterocolitis (NEC), but may increase the risk of diffuse white matter injury (DWMI) in newborns exposed to hypoxia at birth and long-term oxygen supplementation. In addition, the rs11549467A allele was found to be an independent protective factor against respiratory distress syndrome (RDS). No significant associations withVEGFASNPs were observed. These findings indicate the potential involvement of the hypoxia-inducible pathway in the pathogenesis of complications of prematurity. Studies with larger sample sizes are needed to confirm these results and explore their clinical implications.