In the present study, we analyzed TCGA and TCPA data to identify genetic or epigenetic alterations, including somatic mutation, promoter methylation, mRNA expression, and copy number alteration, which are associated with elevated pSTAT3(Y705) expression in HNSCC in order to identify events that contribute to STAT3 activation in this malignancy. The gene discussed is STAT3; the disease is head and neck squamous cell carcinoma.