This study investigates 1) IL-8 expression in surgical specimens of HNSCC and its relationship with clinicopathological factors, 2) the co-operative effects of IL-8 and inflammatory mediators in HNSCC progression; 3) the relationship between the MAPK pathway and the expression of IL-8, and 4) the question of whether the silencing of IL-8 by siRNA affects inflammatory mediators and p38 MAPK, JNK and ERK pathways in HNSCC. This evidence concerns the gene CXCL8 and head and neck squamous cell carcinoma.