In this report, we discover that both Ajuba and SP1 are highly expressed in PDAC tissue and their expression is positively correlated; mechanistically, Ajuba functions as a novel co-activator of SP1 to induce EGFR and IGF1R expression and to promote pancreatic cancer cell growth; moreover, Ajuba itself is a direct target gene of SP1. This evidence concerns the gene EGFR and pancreatic neoplasm.