The　production　of　hydrogen　peroxide　(H2O2)　plays　an　important　role　in　human　lives.　Currently　applying　the　two-electron　oxygen　reduction　reaction　(2e-　ORR)　to　synthesis　of　H2O2　is　regarded　as　a　promising　strategy　to　substitute　the　traditional　anthraquinone　method;however,　design　of　efficient　2e-　ORR　catalysts　remains　difficulties.　Inspired　by　superoxide　dismutase,　which　can　covert　superoxide　(•O2–)　to　H2O2.　We　design　eight　types　of　2e-　ORR　catalysts　in　which　Ni　is　embedded　on　defective　boron　nitride　(h-BN)　which　coordinates　with　non-metal　atoms　(B,　N,　O,　S)　doping　to　imitate　the　active　center　of　superoxide　dismutase.　Density　functional　theory　(DFT)　computations　demonstrate　that　NiN2S2/BN　has　the　most　favorable　2e-　ORR　catalytic　performance　with　the　overpotential　of　0.11　V.　Especially,　the　competitive　4e-　ORR　pathway　can　be　significantly　suppressed,　as　indicated　by　favorable　thermodynamics　with　more　positive　Gibbs　free　energies　of　O*　above　3.52　eV.　Besides,　coordination　environments　change　induced　different　adsorption　behavior　of　O2,　electron　density　around　Ni,　and　work　function　are　unveiled.　Our　work　is　expected　to　provide　useful　understanding　for　development　of　novel　high-efficiency　h-BN-based　single-atom　catalysts　for　2e-　ORR.　©　2022　Elsevier　B.V.