These studies identified C188-9, which binds to STAT3 with high affinity and is more potent than C188 in inhibiting STAT3 binding to its pY-peptide ligand, in inhibiting cytokine-stimulated pSTAT3, in reducing constitutive pSTAT3 activity in UM-SCC-17B, a radioresistant HNSCC cell line, and in inhibiting anchorage dependent and independent growth of these cells. Here, STAT3 is linked to head and neck squamous cell carcinoma.