Fisetin is an effective compound extracted from lacquer which has been used in the treatment of variousdiseases. Preliminary data indicate that it also exerts specific anti-cancer effects. However, the manner in whichfisetin regulates cancer growth remains unknown. In this study, we elucidated interference of fisetin with targetsof the nuclear factor κB signal transduction pathway activated by Epstein-Barr virus encoding latent membraneprotein 1 (LMP1)in nasopharyngeal carcinoma (NPC) cells, Results showed that fisetin inhibited the survivalrate of CNE-LMP1 cells and NF-κB activation caused by LMP1. Fisetin also suppressed nuclear translocationof NF-κB (p65) and IκBα phosphorylation, while inhibiting CyclinD1, all key targets of the NF-κB signaltransduction pathway. It was suggested that interference effects of fisetin with signal transduction activated byLMP1 encoded by the Epstein-Barr virus may play an important role in its anticancer potential.