Aim: To elucidate the interference effect of epigallocatechin-3-gallate (EGCG) on targets of nuclear factor _B (NF-_B) signal transduction pathway activated by EB virus encoded latent membrane protein 1 (LMP1) in nasopharyngeal carcinoma (NPC) cell lines. Methods: The survival rates of CNE1 and CNE-LMP1 cell lines after the EGCG treatment were determined by MTT assay. NF-_B activation in CNE1 and CNE-LMP1 cells after EGCG treatment was analyzed by promoter luciferase reporter system. And then nuclear translocation of NF-_B (p65) after the EGCG treatment was analyzed by immunofluorescence and western blotting. Meanwhile, the changes of I_B_ phosphorylation were observed after the EGCG treatment. EGFR promoter activity was analyzed by promoter luciferase reporter system and EGFR phosphorylation was observed by western blotting after the EGCG treatment. Results: EGCG inhibited the survival rates of CNE1 and CNE-LMP1 cells and NF-_B activation caused by LMP1 in CNE-LMP1 cells. EGCG also suppressed the nuclear translocation of NF-_B (p65) and I_B_ phosphorylation. Meanwhile, EGCG inhibited EGFR promoter activity and EGFR phosphorylation. Conclusions: EGCG inhibited not only the dose-dependent survival rate of NPC cells, but also the dose-dependent activation of NF-_B. This inhibition of LMP1-caused NF-_B activation was mediated via the phosphorylative degradation of its inhibitory protein I_B_, and then EGCG inhibited EGFR activity which was a downstream gene from NF-_B. This study suggests that interference effect of EGCG on targets of signal transduction pathway plays an important role in the anticancer function.