Chidamide is a histone deacetylase inhibitor that increases histone H3 acetylation levels in LoVo and HT-29 colon cancer cells at concentrations as low as 4 μM. Additionally, chidamide affects the activation of oncogenic signaling kinases by dose-dependently reducing phosphorylated Akt, mTOR, p70S6k, Raf, and Erk1/2 protein expression in colon cancer cells. Furthermore, chidamide treatment dose-dependently upregulates p21 protein expression, downregulates Cdk4, and induces cell cycle arrest at the G0/G1 phase.