Protein–protein interaction (PPI) is very important for various biological processes and has given rise to a series of prediction-computing methods. In spite of different computing methods in relation to PPI prediction, PPI network projects fail to perform on a large scale. Aiming at ensuring that PPI can be predicted effectively, we used a deep neural network (DNN) for the study of PPI prediction that is based on an amino acid sequence. We present a novel DNN-PPI model with an auto covariance (AC) descriptor and a conjoint triad (CT) descriptor for the prediction of PPI that is based only on the protein sequence information. The 10-fold cross-validation indicated that the best DNN-PPI model with CT achieved 97.65% accuracy, 98.96% recall and a 98.51% area under the curve (AUC). The model exhibits a prediction accuracy of 94.20–97.10% for other external datasets. All of these suggest the high validity of the proposed algorithm in relation to various species.