Our findings support the notion in several ways: (1) HES4 binds to the promoter region of BEST4; (2) BEST4 colocalises with HES4 and TWIST1 in the nucleus of cells, and protein-protein interactions; (3) the BEST4 inhibitory role in EMT exhibits upregulation of epithelial TJP1 and E-cadherin, and downregulation of mesenchymal VIM and TWIST1 in CRC; and finally (4) low BEST4 mRNA levels were significantly correlated with malignant lesions and worse outcomes of CRC patients. This evidence concerns the gene BEST4 and colorectal carcinoma.