Cerebral ischemic stroke (IS) is a disease presenting high morbidity and mortality rates worldwide. Understanding of the pathogenesis underlying IS may facilitate the development of effective clinical therapeutic strategies and improve the prevention of this disease, decreasing its occurrence rate. Epigenetic alterations have recently attracted attention as possible mechanisms underlying IS. Additionally, tumor protein p53 (TP53) was identified to be involved in the pathophysiology of cerebral stroke. In the present study, the methylation status of the TP53 promoter was investigated in patients with IS and in age‑matched healthy controls. The methylation status of the promoter of TP53 was significantly increased in patients with IS compared with healthy subjects. Additionally, the methylation level of the TP53 promoter was identified to be associated with carotid intima‑media thickness, the degree of carotid atherosclerosis and the circulating levels of homocysteine in peripheral blood. The present findings may improve the understanding of the role of the epigenetic modifications of the TP53 promoter in IS pathogenesis.