In this study, we demonstrated a part of crosstalk between fibroblasts and cancer cells that enhanced the invasiveness of cancer cells, IL8-induced activation of STAT3 signaling pathway as a key promoter to elevated MMP1 level in fibroblasts that supports the migration and invasion of head and neck squamous cell carcinoma (HNSCC) cells by extracellular matrix degradation. This evidence concerns the gene CXCL8 and cancer.