Our study highlights a persistently dysregulated cytokine milieu in HNSCC patients, marked by decreased pro-inflammatory and immunomodulatory mediators (IFN-γ, TNF-β, CCL3, CCL20, CXCL1, TWEAK, SCF, and LIF) compared to healthy controls. The gene discussed is TNFSF12; the disease is head and neck squamous cell carcinoma.