Biomolecular networks such as protein–protein interaction networks provide a static picture of the interplay of genes and their products, and, consequently, they fail to capture dynamic changes taking place during the development of complex diseases. KeyPathwayMiner is a software platform designed to fill this gap by integrating previous knowledge captured in molecular interaction networks with OMICS datasets (DNA microarrays, RNA sequencing, genome-wide methylation studies, etc.) to extract connected subnetworks with a high number of deregulated genes. This protocol describes how to use KeyPathwayMiner for integrated analysis of multi-omics datasets in the network analysis tool Cytoscape and in a stand-alone web application available at https://keypathwayminer.compbio.sdu.dk.