Prolonged perinatal asphyxia (PA) may cause hypoxic-ischemic damage to the brain. The aim of this study was to investigate the brain diffusion changes of patients with PA and examine the relationship with brain damage. This retrospective study included 55 patients diagnosed with PA, separated into mild and severe PA groups. For the evaluation of brain damage in all the study neonates, brain and diffusion MRI scans were performed using a 3T device. The scans were taken between 5 and 10 days postnatal, after completion of hypothermia treatment, in accordance with the standard clinical protocol of our institution. Apparent diffusion coefficient (ADC) values of the lentiform nucleus, thalamus, frontal white matter, and posterior limbs of the internal capsule were measured. Minitab package programs and SPSS version 20.0 software were used for statistical analysis and graphic drawing. Spearman's rank correlation analysis was used. The bilateral lentiform nucleus, thalamus, frontal white matter, and posterior limbs of the internal capsule ADC values were significantly higher in the severe PA group than in the mild PA group. In neonates with severe perinatal asphyxia, brain damage can be evaluated on diffusion-weighted imaging (DWI) of the cerebral deep white matter and basal ganglia. DWI, imaging with conventional brain MRI comes to the fore in clinical importance in PA patients.