MOTIVATION: Genetically engineering food crops involves introducing proteins from other species into crop plant species or modifying already existing proteins with gene editing techniques. In addition, newly synthesized proteins can be used as therapeutic protein drugs against diseases. For both research and safety regulation purposes, being able to assess the potential toxicity of newly introduced/synthesized proteins is of high importance. RESULTS: In this study, we present ToxDL, a deep learning-based approach for in silico prediction of protein toxicity from sequence alone. ToxDL consists of (i) a module encompassing a convolutional neural network that has been designed to handle variable-length input sequences, (ii) a domain2vec module for generating protein domain embeddings and (iii) an output module that classifies proteins as toxic or non-toxic, using the outputs of the two aforementioned modules. Independent test results obtained for animal proteins and cross-species transferability results obtained for bacteria proteins indicate that ToxDL outperforms traditional homology-based approaches and state-of-the-art machine-learning techniques. Furthermore, through visualizations based on saliency maps, we are able to verify that the proposed network learns known toxic motifs. Moreover, the saliency maps allow for directed in silico modification of a sequence, thus making it possible to alter its predicted protein toxicity. AVAILABILITY AND IMPLEMENTATION: ToxDL is freely available at http://www.csbio.sjtu.edu.cn/bioinf/ToxDL/. The source code can be found at https://github.com/xypan1232/ToxDL. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.