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Colorectal cancer (CRC), one of the leading causes of cancer related deaths worldwide is an outcome of both genetic and epigenetic changes in colonic epithelia leading to the formation of adenocarcinomas. Histone deacetylases (HDACs) through their key roles in regulation of cellular processes, are associated with the development and progression of cancer. Thus, in this regard, HDAC inhibitors have become promising therapeutic targets. These inhibitors induce cell cycle arrest, differentiation, autophagy and apoptotic cell death by inhibiting multiple signaling pathways. Suberoylanilide hydroxamic acid (SAHA), a second generation HDAC inhibitor has been approved by US‐FDA for the treatment of cutaneous T‐Cell lymphoma, however its anti‐cancerous effects against colorectal cancer is still unknown. Also, essential dietary element Selenium (Se) has been found to have an important role in CRC prevention …