Therefore, for the first time, we proposed and tested the hypothesis that let-7c inhibits tumor cell growth, migration, and EMT by directly targeting IGF1R and HMGA2. Our findings identified let-7c as a tumor suppressor miRNA and provided new insights into the molecular function of let-7c and its target genes IGF1R and HMGA2, suggesting new therapeutic targets in HNSCC. The gene discussed is IGF1R; the disease is head and neck squamous cell carcinoma.