In summary, the findings of our study reveal a significant association between ENOSF1 rs2612091-CC genotype ACT haplotype in the TYMS/ENOSF1 gene region with DFS in CRC patients under capecitabine-based adjuvant therapy, suggesting their potential as promising genetic biomarkers of treatment prognosis. This evidence concerns the gene ENOSF1 and colorectal carcinoma.