Tuning the electronic structure of single atom catalysts (SACs) is an effective strategy to promote the catalytic activity in peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs). Herein, a series of Fe-based SACs with S1/2/3/4-coordination numbers on graphene were designed to regulate the electronic structural of SACs at molecular level, and their effects on PMS activation were investigated via density function theory (DFT). The calculation results demonstrate that the electron structure of the active center can be adjusted by coordination environment, which further affects the activation of PMS. Among the studied Fe-SX-C4−X catalysts, with the increase of the S coordination number, the electron density of the Fe-SX-C4−X active center was optimized. The active center of the Fe-S4-C0 catalyst has a largest positive charge density, exhibiting the highest number of electron transfer. It also has a lower kinetic energy barrier (0.28 eV) for PMS dissociation. Organic pollutant such as bisphenol A (BPA) can achieve stable adsorption on Fe-SX-C4−X catalysts, which is conducive to subsequent oxidation by radicals. The dual index ∆f(r) indicates that the para-carbon atom of the hydroxyl group on the benzene ring of BPA is vulnerable to radical attack. This study highlights a theoretical support and a certain guide for designing efficient SACs to activate PMS.