Predicting the cofactors of oxidoreductases plays an important role in inferring their catalytic mechanism. Feature extraction is a critical part in the prediction systems, requiring raw sequence data to be transformed into appropriate numerical feature vectors while minimizing information loss. In this paper, we present an amino acid composition distribution method for extracting useful features from primary sequence, and the k-nearest neighbor was used as the classifier. The overall prediction accuracy evaluated by the 10-fold cross-validation reached 90.74%. Comparing our method with other eight feature extraction methods, the improvement of the overall prediction accuracy ranged from 3.49% to 15.74%. Our experimental results confirm that the method we proposed is very useful and may be used for other bioinformatical predictions. Interestingly, when features extracted by our method and Chou's amphiphilic pseudo-amino acid composition were combined, the overall accuracy could reach 92.53%.