Colorectal cancer (CRC), one of the leading cause of cancer deaths around the world, is mainly from genetic and epigenetic changes in colon epithelial cells.1 5‐fluorouracil (5‐FU), a common pyrimidine analogue for CRC, could block thymidylate synthetase and further inhibit the synthesis of DNA and RNA.2 However, clinical treatment with 5‐FU for CRC is restricted due to its chemoresistance and results in poor prognosis.3 Therefore, understanding the mechanism of the resistance to 5‐FU is crucial to the chemotherapy of CRC. The gene discussed is TYMS; the disease is colorectal carcinoma.