SignificanceTransformation by the proto-oncogene MYC causes dysregulation of the pre-mRNA splicing reaction in cancer, but it is not known how mRNA isoform changes are directed by MYC. Here, we use bioinformatics to identify a splicing event in another proto-oncogene, HRAS, that is regulated by MYC across multiple tumor types. We identify splicing regulators, hnRNPs H and F, that control this HRAS exon by binding to enhancer elements within its downstream intron. Additional pan-cancer bioinformatic analyses show hnRNP H expression to be anticorrelated with MYC hallmarks, consistent with the reduced splicing of the HRAS exon in MYC-driven cancer. These findings uncover mechanisms by which MYC can alter splicing in cancer cells and provide molecular targets for potential therapeutics.