SUMMARY: Somatic mutations and gene fusions can produce immunogenic neoantigens mediating anticancer immune responses. However, their computational prediction from sequencing data requires complex computational workflows to identify tumor-specific aberrations, derive the resulting peptides, infer patients' Human Leukocyte Antigen types and predict neoepitopes binding to them, together with a set of features underlying their immunogenicity. Here, we present nextNEOpi (nextflow NEOantigen prediction pipeline) a comprehensive and fully automated bioinformatic pipeline to predict tumor neoantigens from raw DNA and RNA sequencing data. In addition, nextNEOpi quantifies neoepitope- and patient-specific features associated with tumor immunogenicity and response to immunotherapy. AVAILABILITY AND IMPLEMENTATION: nextNEOpi source code and documentation are available at https://github.com/icbi-lab/nextNEOpi. CONTACT: [email protected] or [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.