Head and neck squamous cell carcinoma is the 6th most common malignancyworldwide. Recently, a link between cancer and inflammation has been found. Mediatingthis relationship are the chemotactic cytokines known as chemokines. CXCL8 (Interleukin-8), a CXC ELR+ Chemokine mainly responsible for neutrophil chemoattraction, has beenimplicated in increased tumor proliferation, migration and angiogenesis. The current studytests the effects of CXCL8 on the tumor proliferation and metastasis. By genetically modifying cells to knockdown or overexpress the CXCL8 gene we tested its biological rolein head and neck cancer progression. Overexpression of CXCL8 in HN4 tumor cells withlow endogenous CXCL8 levels was found to increase tumor growth, as judged by cellcounting and MTT assays. Conversely, RNAi-mediated knockdown of CXCL8 expressionin HN12 cells, which express high levels of this chemokine, resulted in a decrease inproliferation. Similarly, overexpression of CXCL8 enhanced migration of HN4 cells invitro, while knockdown inhibited HN12 cell migration and invasion through a basementmembrane substitute. Taken together, these findings support the hypothesis that CXCL8affects multiple processes involved in head and neck cancer tumor progression. The datasuggest that CXCL8 is a potential therapeutic target for head and neck, and other, cancers.