In chromosome, acetylation and deacetylation of histones play one of important roles in gene regulation. Acetylation of the specific histone lysine residues catalyzed by histone acetyltransferases (HATs) correlates with an open, decondensed chromatin structure and gene transcription, while deacetylation of histone correlates with chromatin condensation and gene repression. Consistent with this, higher histone deacetylase (HDAC) activity is found in a large number of human malignancies and suppresses transcriptional expression of tumor suppressor genes. Histone deacetylase inhibitors (HDACi) as promising anti-cancer agents are due to inhibition of cell survival and induction of apoptosis in cancers. Moreover, HDACi can regulate p53 function via induction of p21 (WAF1) and possesses anti-tumor activities through regulation of α-tubulin, HIF-1α and HSP90. Our pipeline of HDACi is in the lead optimization phase and is going to demonstrate its anti-cancer efficacy in-vitro and in-vivo.