The p53-family member, p63 is a transcription factor that influences cellular adhesion, motility, proliferation, survival and apoptosis, and has a major role in regulating epithelial stem cells. Expression of p63 is often dysregulated in squamous cell carcinomas of the head and neck. In this study we show that p63 induces the expression of the basal epithelial transcription factor, Basonuclin 1. Basonuclin 1 is an unusual transcription factor that interacts with a subset of promoters of genes that are transcribed by both RNA polymerase-I and -II and has roles in maintaining ribosomal biogenesis and the proliferative potential of immature epithelial cells. Chromatin immunoprecipitation and reporter assays demonstrate that Basonuclin 1 is a direct transcriptional target of p63 and we also show that up-regulation of Basonuclin 1 is a common event in squamous cell carcinomas of the head and neck. These data identify a new transcriptional programme mediated by p63 regulation of the Basonuclin 1 transcription factor in squamous cell carcinomas and provide a novel link of p63 with the regulation of ribosomal biogenesis in epithelial cancer. (C) 2011 Elsevier Ltd. All rights reserved.