To screen for modulators of TNFα-induced NF-κB prosurvival signaling, we developed an HPV− HNSCC cell line stably expressing NF-κB promoter response elements linked to a β-lactamase reporter gene (5) and performed an RNA interference (RNAi) screen for targets resulting in inhibition of TNFα-induced NF-κB activation, and cell viability. The gene discussed is NFKB1; the disease is head and neck squamous cell carcinoma.