AbstractMotivationTo complement experimental efforts, machine learning-based computational methods are playing an increasingly important role to predict human–virus protein–protein interactions (PPIs). Furthermore, transfer learning can effectively apply prior knowledge obtained from a large source dataset/task to a small target dataset/task, improving prediction performance.ResultsTo predict interactions between human and viral proteins, we combine evolutionary sequence profile features with a Siamese convolutional neural network (CNN) architecture and a multi-layer perceptron. Our architecture outperforms various feature encodings-based machine learning and state-of-the-art prediction methods. As our main contribution, we introduce two transfer learning methods (i.e. ‘frozen’ type and ‘fine-tuning’ type) that reliably predict interactions in a target human–virus domain based on training in a source human–virus domain, by retraining CNN layers. Finally, we utilize the ‘frozen’ type transfer learning approach to predict human–SARS-CoV-2 PPIs, indicating that our predictions are topologically and functionally similar to experimentally known interactions.Availability and implementationThe source codes and datasets are available at https://github.com/XiaodiYangCAU/TransPPI/.Supplementary informationSupplementary data are available at Bioinformatics online.