In this work, a novel strategy for Fenton activity improvement of Cu 2 X was reported, in which the local electron density of Cu sites was regulated via manipulation of simple chalcogen elements (O, S, and Se). Among them, Cu 2 Se catalysts show excellent catalytic activity to activate H 2 O 2 for the complete removal of ofloxacin (10 mg/L) at an initial pH of 6.5 within 120 min. Radical scavenger experiments and electron spin resonance spectroscopy confirm that • OH radicals are the primary oxygen reactive species to drive ofloxacin degradation. In addition, density functional theory calculations further proved that electrons would migrate from X and accumulate on Cu active sites in the order Se > S > O. Compared with Cu 2 O and Cu 2 S, the highly concentrated electron density of Cu atoms in Cu 2 Se not only decreased the activation energy of the Fenton-like reaction but also boosted the Cu 2+ /Cu + cycle with the generation of more • OH radicals (18-66 μm) and the maintenance of high stability of catalysts, leading to excellent catalytic activity and application potential. We believe this work will lay the foundation for designing excellent Fenton catalysts for practical applications since developing a heterogeneous Fenton system with the highest oxidation efficiency has always been the long-term goal in this field.