This　work　disclosed　the　trade-off　effect　of　two　metal　sites,　which　display　distinct,　key　functionalities　in　naturally　occurring　and　artificial　catalysts　for　developing　an　advanced　CO2reduction　system.　To　exploit　the　metal-organic　frameworks　(MOFs)　as　advanced　catalysts,　we　prepared　a　series　of　Prussian　blue　analogues　(FeNixPBAs)　of　tunable　Ni/Fe　molar　ratio　without　changing　the　oxidation　state　of　Fe　and　Ni　for　use　as　a　photocatalyst　in　the　CO2reduction　reaction　(CRR).　The　FeNi0.66PBA　gives　a　superior　CO　yield　rate　(14.28　mmol·g-1·h-1)　with　nearly　100%　CO　selectivity,　but　the　PBA　would　be　basically　CRR-inactive　without　either　Ni　or　Fe.　Experimental　and　calculation　studies　demonstrate　that　Fe　and　Ni　display　distinct　functionalities.　Specifically,　Fe　is　an　efficient　mediator　that　boosts　the　electron　transfer　both　from　the　photosensitizer　to　FeNixPBA　and　from　FeNixPBA　to　CO2,　and　Ni　serves　as　the　active　site　for　CO2adsorption　and　reduction.　Intriguingly,　when　there　is　already　sufficient　Ni　in　the　catalyst,　further　increase　of　the　Ni　content　gives　marginal　gains　in　the　CO2adsorption　affinity　that　cannot　offset　the　weakened　electron　transfer　due　to　the　Ni　excess.　The　findings　can　help　advance　the　design　of　bimetallic　MOF　catalysts　that　mimic　naturally　occurring　bimetallic　catalysts.　©　2022　American　Chemical　Society.　All　rights　reserved.