In this study, we proved for the first time that p70S6K promoted EMT and the metastasis of HNSCCs based on the following findings: 1) paired high-metastatic HNSCC cells underwent EMT in parallel with p70S6K upregulation and activation; 2) overexpression of p70S6K induced EMT and promoted the migration of HNSCC cells; 3) IL-6 activated p70S6K, and the knockdown of p70S6K attenuated IL-6-induced EMT and cell migration. Here, IL6 is linked to head and neck squamous cell carcinoma.