Summary: Interpretation and prioritization of candidate hits from genome-scale screening experiments represent a significant analytical challenge, particularly when it comes to an understanding of cancer relevance. We have developed a flexible tool that substantially refines gene set interpretability in cancer by leveraging a broad scope of prior knowledge unavailable in existing frameworks, including data on target tractabilities, tumor-type association strengths, protein complexes and protein-protein interactions, tissue and cell-type expression specificities, subcellular localizations, prognostic associations, cancer dependency maps, and information on genes of poorly defined or unknown function. Availability: oncoEnrichR is developed in R, and is freely available as a stand-alone R package. A web interface to oncoEnrichR is provided through the Galaxy framework (https://oncotools.elixir.no). All code is open-source under the MIT license, with documentation, example datasets and and instructions for usage available at https://github.com/sigven/oncoEnrichR/ Contact: sigven@ifi.uio.no