Atherosclerosis (AS) is the primary cause of cardiovascular disorders, which lead to one-third of all death globally. However, the atherosclerosis process remains elusive due to the lack of appropriate analytical methods. Herein, we present the first nanoflare-based DNA sensor that could report the distribution of ClO⁻ (a typical marker of AS) in the atherosclerotic plaques. ClO⁻-responsive phosphorothioate (PS) was inserted into DNA, which was then assembled with a gold nanoparticle (AuNP) core to form a ClO⁻-specific nanoflare probe. The hydrolysis between PS and ClO⁻ triggered fluorescence turn-on of the probes, showing excellent sensitivity (as low as 8.51 nM) and specificity for ClO⁻ detection. In addition, the nanoflare probes exhibit superior performance in tracing the variations of endogenous and exogenous ClO⁻ in living RAW264.7 cells. After intravenous injection, the efficient accumulation of probes and fluorescence signal enhancement were observed in the atherosclerotic plaques of AS model mice. The nanoflare probes possess significant feasibility in the precise identification of atherosclerotic plaques, which holds tremendous implications for clinical diagnosis, mechanism study, and assessment of therapeutic outcomes associated with AS.