Hemodynamic fluctuations during hemodialysis therapy may result in brain damage, such as white matter hyperintensity (WMH). Cerebral blood flow (CBF) changes occurred before the appearance of WMH. To explore changes in CBF and white matter in hemodialysis patients, patients underwent twice structural and arterial spin-labeling MRI examinations at an interval of three years. Based on the changes in CBF between the baseline and follow-up groups, the hemodialysis patients were divided into two subgroups, increased CBF group and decreased CBF group. Our results showed that patients undergoing hemodialysis exhibited increased cerebral watershed white matter hyperintensities, deep WMH, and periventricular. Among HC, hemodialysis baseline, and follow-up patients, the CBF of gray matter, white matter, and whole matter showed no obvious differences. The CBF of patients with decreased CBF was higher than that of HC at baseline and lower than that of HC at follow-up. Compared with the increased CBF group, obvious development of deep WMH was found in the decreased CBF group for the gray matter, white matter, and whole matter. Therefore, WMH in hemodialysis patients were distributed in the deep white matter, periventricular white matter and cerebral watershed (CW), and progressed with the extension of hemodialysis duration. CBF in hemodialysis patients could manifest as both increased and decreased, and WMH in patients with decreased CBF developed severely with prolongation of hemodialysis duration.