BRAF V600E is the activating driving mutation in 10% of CRC and correlates with poor prognosis, however targeted therapy against the mutation was proven ineffective and first-line treatment includes cytotoxic chemotherapy [1]; thus, we investigated the role of the HH-GLI and NOTCH signaling pathways in 5-FU chemotherapy resistance in BRAF mutant HT29 cells. This evidence concerns the gene GLI1 and colorectal carcinoma.