Since the epigenetic alteration in tumor cells can be reversed by the dietary polyphenol quercetin (Q) orbutyrate (B) with chemopreventive activity, suggesting that Q or B can be used for chemopreventive as well astherapeutic agent against tumors. In this study the polyphenol flavonoid quercetin (Q) or sodium butyrate (B)suppressed human esophageal 9706 cancer cell growth in dose dependent manner, and Q combined with B (Q+B)could further inhibit Eca9706 cell proliferation than that induced by Q or B alone, compared with untreatedcontrol group (C) in MTT assay. The reverse expressions of global DNMT1, NF-κBp65, HDAC1 and Cyclin D1were down-regulated, while expressions of caspase-3 and p16INK4α were up-regulated, compared with the Cgroup in immunoblotting; the down-regulated HDAC1-IR (-immunoreactivity) with nuclear translocation, andup-regulated E-cadherin-IR demonstrated in immunocytochemistry treated by Q or B, and Q+B also displayedfurther negatively and positively modulated effects compared with C group. The order of methylation specific(MS) PCR of p16INK4α: C>B/Q>Q+B group, while the order of E-cadherin expression level was contrary,Q+B>Q/B>C group. Thus, Q/B, especially Q+B display reverse effect targeting both altered DNA methylationand histone acetylation, acting as histone deacetylase inhibitor mediated via epigenetic-NF-κB cascade signaling.