Single atom catalysts (SACs) have attracted great attention, yet the quest for highly-efficient catalysts is driven by the current obstacles of ambiguous structure-performance relationship. Here, we report a nature keratin-based Fe-S₁N₃ SACs with ultrathin two-dimensional (2D) porous carbon nanosheets structure, by controlling the active center through the precise coordination of sulfur and nitrogen. Compared with natural silk-based Fe-N₄ catalyst, the Fe-S₁N₃ SACs exhibit excellent Fenton-like oxidation degradation ability. X-ray absorption fine structure (XAFS) and electron paramagnetic resonance (EPR) results confirm that S doping is conducive to electron transfer, to accurately generate ·OH with high oxidative degradation capacity at the active site. Therefore, the optimized Fe-S₁N₃ catalyst showed higher oxidation degradation activity for organic pollutant substrates (methylene blue (MB), Rhodamine B (RhB) and phenol), significantly superior to Fe-N₄ samples. This work is devoted to the treatment and application of natural fibers, which provides a novel method for the synthesis of SACs and the regulation of atomic coordination environment.