Highly hydrophilic extracellular polymeric substance (EPS) with gel-like structure seriously plagues the development of sludge deep dewatering. Oxysulfur radicals-based oxidation driven by iron-bearing mineral proposes a promising strategy for effective EPS decomposition. However, the transformation and involved interaction mechanisms of aromatic proteins are still controversial due to the complex EPS structure. Herein, sulfite mediated siderite (denoted as Fe(II)/S(IV)) was developed for targeted transformation aromatic amino acids in EPS oxidation to strengthen sludge solid-liquid separation. The enhanced sludge dewaterability were benefited from the Fe(II)/S(IV) bonded interaction assisted by Fe 3+ /Fe 2+ as redox interface that facilitating the release of intracellular bound water via diminish the hydrophily and bind strength with solid protons. The amide region nitrogen of aromatic amino acids (especially tyrosine and tryptophan) originating from EPS presented looser structure and lower spatial site resistance, which were attributed to the exposure of hydrophobic sites in amino groups after Fe(II)/S(IV) treatment. Furthermore, the effective decline of aromatic amino acids in inner layer-EPS (loosely bound EPS and tightly bound EPS) was directed from Fe-N targeted interaction by triggering a series of sulfate-based radical chain reactions. The good correlation between electron transfer amount (R 2 = 0.926) and Fe-N (R 2 = 0.925) with bonding interaction demonstrated that the complexation of aromatic amino acids with Fe sites on siderite/sulfite via Fe-N bonds, accounting for efficient sludge solid-liquid separation. This study deepens the understanding of sludge organic matter targeted transformation and provides a tactic for iron-based conditioning of sludge.