Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor. We here investigated its effects on proliferationand apoptosis of the CNE2 carcinoma cell line, and attempted to establish genome-wide DNA methylationalteration due to differentially histone acetylation status. After cells were treated by TSA, the inhibitory rate ofcell proliferation was examined with a CCK8 kit, and cell apoptosis was determined by flow cytometry. Comparedto control, TSA inhibited CNE2 cell growth and induced apoptosis. Furthermore, TSA was found to inducegenome-wide methylation alteration as assessed by genome-wide methylation array. Overall DNA methylationlevel of cells treated with TSA was higher than in controls. Function and pathway analysis revealed that manygenes with methylation alteration were involved in key biological roles, such as apoptosis and cell proliferation.Three genes (DAP3, HSPB1 and CLDN) were independently confirmed by quantitative real-time PCR. Finally,we conclude that TSA inhibits CNE2 cell growth and induces apoptosis in vitro involving genome-wide DNAmethylation alteration, so that it has promising application prospects in treatment of NPC in vivo. Although manyunreported hypermethylated/hypomethylated genes should be further analyzed and validated, the pointers tonew biomarkers and therapeutic strategies in the treatment of NPC should be stressed.