MOTIVATION: Rapid developments of single-cell RNA sequencing technologies allow study of responses to external perturbations at individual cell level. However, in many cases, it is hard to collect the perturbed cells, such as knowing the response of a cell type to the drug before actual medication to a patient. Prediction in silicon could alleviate the problem and save cost. Although several tools have been developed, their prediction accuracy leaves much room for improvement. RESULTS: In this article, we propose scPreGAN (Single-Cell data Prediction base on GAN), a deep generative model for predicting the response of single-cell expression to perturbation. ScPreGAN integrates autoencoder and generative adversarial network, the former is to extract common information of the unperturbed data and the perturbed data, the latter is to predict the perturbed data. Experiments on three real datasets show that scPreGAN outperforms three state-of-the-art methods, which can capture the complicated distribution of cell expression and generate the prediction data with the same expression abundance as the real data. AVAILABILITY AND IMPLEMENTATION: The implementation of scPreGAN is available via https://github.com/JaneJiayiDong/scPreGAN. To reproduce the results of this article, please visit https://github.com/JaneJiayiDong/scPreGAN-reproducibility. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.