In order to explore the usage bias of redox cofactors,we analysed the cofactor usage in forty species by bioinformatics method and found the distribution rule: about 90% redox enzymes used organic cofactors in archaeon and prokaryotes and about 78% redox enzymes used organic cofacotrs in eukaryotes.In order to explain above rule,we had done the following researches.First,we analysed the redox reaction equations.The results indicated that 28.5% organic enzymes reactions need oxygen and 63.2% metallic enzymes reactions need oxygen.Therefore,we inferred that the emergence of oxygen was one of the most important reasons probably that induced the increase of usage frequence for metallic cofactors.Secondly,we analysed the chemical characters of small molecules participating in the redox reactions.The results indicated that the small molecules of organic reactions group were much bigger and hydrophilic.Therefore,we inferred that metallic cofactors were suitable for hydrophobic environment.