The aim of this study is to investigate the frequency of six tag SNPs (single nucleotide polymorphisms) within specific genes (F2, F5, F7, MTHFR, NOS2A, PAI 2-1, PAI 2-2, and PAI 3-3): F2 (rs1799963), F5 (rs6025), F7 (rs6046), NOS 2 (rs1137933), PAI 2 (SERPINB2) (rs6103), MTHFR (rs1801133). The study also investigates their association with the development and severity of HIE. The genes F2, F5, and F7 code for proteins involved in blood clotting. MTHFR is a gene that plays a significant role in processing amino acids, the fundamental building blocks of proteins. NOS2A, PAI 2-1, PAI 2-2, and PAI 3-3 are genes involved in the regulation of various physiological processes, such as the relaxation of smooth muscle, regulation of central blood pressure, vasodilatation, and synaptic plasticity. Changes in these genes may be associated with brain injury. This retrospective study included 279 participants, of which 132 participants had Hypoxic–Ischemic Encephalopathy (HIE) and 147 subjects were in the control group. Our study found that certain genetic variants in the rs61103 and rs1137933 polymorphisms were associated with hypoxic–ischemic encephalopathy (HIE) and the findings of the magnetic resonance imaging. There was a correlation between Apgar scores and the degree of damage according to the ultrasound findings. These results highlight the complex relationship between genetic factors, clinical parameters, and the severity of HIE.