Background: The prognostic predict biomarkers are important in oral squamous cell carcinoma (OSCC). We investigated the expression patterns and quantitation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in OSCC patients. Among OSCC patients with recurrence and metastasis, the expression percentages of HIF-1α and VEGF also were analyzed. Methods: Thirty-eight patients (8 hyperkeratosis, 30 oral squamous cell carcinoma) were included in this study. In the follow-up period, 5 OSCC patients had metastasis and 12 OSCC patients had local recurrence. We used computer-assisted image processing to analyze immunohistochemistry (IHC). The quantitative analysis of IHC slides, including upper-layer epithelium (U) and lower-layer epithelium (L), was calculated. Results: We found homogeneous expression of VEGF in the epithelium. However, two patterns of HIF-1α expression were observed: homogeneous and heterogeneous. The highest U + L layer percentage in HIF-1α and VEF expression had significant association in tumor metastasis and recurrence (p156.4%, and the survival rate was poor (p
