Electrocatalytic 2e⁻ oxygen reduction reaction (2e⁻ ORR) is a promising approach to producing H₂O₂ at ambient temperature and pressure especially in acidic media, which, however, is hindered by the high cost of precious metal-based electrocatalysts. Hence, the development of efficient earth-abundant electrocatalysts and reaction mechanism exploration for H₂O₂ production by 2e⁻ ORR in acidic solution are critically important but remain challenging at present. In this work, NiSe₂ has been developed as a novel and high-performance 2e⁻ ORR electrocatalyst in acidic media, moreover, using nickel chalcogenides as the models, the influence of different anion species (Se₂²⁻, S₂²⁻, and O²⁻) on 2e⁻ ORR electrocatalytic performance of the catalysts has been investigated. The synthesized NiSe₂ exhibits outstanding 2e⁻ ORR performance of high selectivity (90%) and long-term durability (12 h). The maximum H₂O₂ concentration of NiSe₂ reaches 988 ppm, which is the highest among all the reported transition metal chalcogenides. This work demonstrates a novel point of view in anion tuning for designing high-efficiency transition-metal-based electrocatalysts for 2e⁻ ORR.