Driver mutations are anticipated to change the gene expression of their related or interacting partners, or cognate proteins. We introduce DEGdriver, a novel method that can discriminate between mutations in drivers and passengers by utilizing gene differential expression at the individual level. Tested on eleven TCGA cancer datasets, DEGdriver substantially outperforms cutting-edge approaches in distinguishing driver genes from passengers and exhibits robustness to varying parameters and protein-protein interaction networks. We further show, through enrichment analysis, that DEGdriver is capable of identifying functional modules or pathways in addition to novel driver genes.