<p>The 5-year survival rate of early-stage hepatocellular carcinoma (HCC) patients remains only 60%, largely due to the inability to achieve ultra-early detection and safe, minimally invasive intervention of its premalignant precursor—high-grade dysplastic nodules (HGDN). Current clinical practice faces an unresolved dilemma: conventional imaging has limited sensitivity for HGDN, no standardized minimally invasive intervention exists, and no integrated platform enables synchronous detection, boundary localization and on-demand intervention, despite HGDN 80.8% 5-year HCC progression rate. To address these core challenges, we developed a multifunctional dual-hairpin DNA polydopamine nano-system (H/R@PDA-GC) targeting miRNA-224, a biomarker consistently upregulated during HGDN malignant transformation.</p><p>This system enables specific detection of miRNA-224 with an ultra-low limit of detection (LOD) of 0.068 pM. Clinically, there is a 3-5-year natural history window from HGDN formation to clinically diagnosable early HCC; thus, this system provides a potential technical tool for the ultra-early warning of HCC at the precancerous stage. It simultaneously activates near-infrared fluorescence for targeted imaging of HGDN to precisely delineate lesion boundaries, and leverages its efficient photothermal conversion capability to achieve effective ablation of HGDN in validated murine models. Both cellular and animal studies confirmed its good in vitro and short-term in vivo biocompatibility, significant anti-inflammatory and antioxidant effects, and therapeutic efficacy, addressing the dual clinical needs of ultra-early detection and safe intervention of premalignant lesions. Consequently, H/R@PDA-GC provides an integrated theranostic strategy, which has potential clinical value for reducing the risk of HCC progression, and lays a foundation for ultra-early intervention of HCC precancerous lesions.</p><p>Clinical trial number. Not applicable. </p> Graphical Abstract <p></p>