Heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) is a secreted protein that releases immobilized fibroblast growth factor-2 (FGF-2) from the extracellular matrix and plays a critical role in FGF bioactivation. In the present study co-localization of FGF-2 and HBp17/FGFBP-1 was observed in oral tissues including normal mucosa, hyperplasia, dysplasia of different degrees and oral squamous cell carcinoma (OSCC). The expression score for HBp17/FGFBP-1, FGF-2 as well as vascular endothelial growth factor A (VEGF-A) became higher with the severity of epithelial dysplasia and was highest in severe dysplasia. The expression of HBp17/FGFBP-1, FGF-2 and VEGF-A showed significant association with microvessel density, but no correlation with TNM stages or OSCC recurrence interval. Our results demonstrated that HBp17/FGFBP-1, like VEGF-A and FGF-2, might also promote the induction of tumor angiogenesis. The strongest expression of angiogenic factors in severe dysplasia suggests a potential point for targeting novel anti-angiogenic therapeutic strategies.