OBJECTIVE: To determine the relationship between heat shock proteins (HSPs) and the proinflammatory, anti-apoptosis mediator NF-kappa-B in squamous cell carcinoma. STUDY DESIGN AND SETTING: CA-9-22 cells were exposed to heat stress to induce the production of HSPs. Immunoblot and reporter gene experiments determined the inducibility of HSP production and the activation of cytokine-induced NF-kappa-B. Immunoblot experiments determined the presence of the inhibitor-κ-B-α (IκBα). RESULTS: CA-9-22 cells can be induced by heat stress to produce HSPs at 100-fold above baseline levels. The induction of HSPs prevents the activation and nuclear translocation of NF-kappa-B despite stimulation with IL-1β and TNF-α. CONCLUSIONS: Constitutive activation of NF-kappa-B is prevented by HSP induction through an increase in IκBα synthesis. SIGNIFICANCE: The induction of HSP70 alters the inflammatory milieu associated with squamous cell carcinoma progression through the inhibition of NF-kappa-B and may ultimately promote apoptosis in head and neck carcinoma.