In this study we presented data about three major points: First, miR-92b overexpression contributes to high clinical stages and poor prognosis of HNSCC patients, second, miR-92b is transcriptionally activated by SP1 and simultaneously promotes its expression, and finally, the SP1/miR-92b positive feedback loop facilitates HNSCC cell migration and invasion in vitro and tumor growth in vivo. Here, SP1 is linked to head and neck squamous cell carcinoma.