Background: Colorectal cancer is considered as one of the most common death causes among cancer types in the developed countries. Methylation in the promoter of genes shows specific patterns, which define the molecular pathogenesis and prognosis of the cancer. Therefore, reversal of DNA methylation constitutes a potential therapeutic target. Coexistence of B-RAF V600E mutation with hypermethylation in the promoter of specific genes and chromosomal instability characterize the serrated pathway of carcinogenesis in colorectal cancer and has been associated with poor prognosis. The purpose of this study was to investigate if inhibition of BRAF V600E mutation by the selective inhibitor Dabrafenib in the RKO cell line has any effect on the methylation phenotype of the Weisenberger’s CIMP panel genes. Materials and methods: RKO cancer cell line was cultured under various conditions of Dabrafenib concentrations, time of treatment, cell passage and culture medium provision. Cells from every condition were counted and the subsequently extracted DNA was modified using sodium bisulfate. The characterization of the methylation phenotype was performed by MS-PCR analysis. Modified genomic DNA from Caco2 cancer cell line was used as a control. Results: Dabrafenib treatment resulted in a 50% inhibition of cell growth rate, independent of the concentration used and has no effect on the methylation status of the genes tested under all conditions. Conclusions: Inhibition of the B-RAFV600E by Dabrafenib was not able to reverse the CIMP phenotype in the RKO cell line.