Through bioinformatics data mining and validation using a panel of 8 normal oral keratinocyte lines and 10 HNSCC cell lines, we identified 6 candidate biomarkers that were differentially expressed, of which 3 (PLAU, FN1, CDCA5) were upregulated and 3 (CRNN, CLEC3B and DUOX1) downregulated in HNSCC. This evidence concerns the gene PLAU and head and neck squamous cell carcinoma.