In the present study, the association between peripheral blood-based HTRA1 methylation and the risk of stroke in the Chinese population was evaluated in an independent case–control study consisting of 190 stroke patients and 190 age- and sex-matched controls and was further verified in a prospective nested case–control study including 139 cases who developed stroke within 2 years after recruitment and 144 matched stroke-free controls from a cohort with a total of 11,151 subjects. Here, HTRA1 is linked to stroke disorder.