Wheat (Triticum aestivum L.) is a global staple food crop, but its production often impacts by abiotic stresses.As one of the main soluble carbohydrates in plants,fructans are not only a vital substance involved in protecting plants against water deficit caused by drought, salinity, high or low temperature, but also a crucial carbon source for the formation of grain yield.The 6-SFT (6-sucrose : fructan fructosyltransferase) is a key enzyme responsible for the fructan biosynthesis in plants.In the present research, we dissected the nucleotide polymorphism of 6-SFT and its relationship with agronomic traits in wheat.Two genetic populations and a natural population consisted of 154historical accessions were used as the plant materials for linkage mapping and association analysis of the target gene.Three copies of 6-SFT were isolated from Hanxuan 10, a drought-tolerant cultivar, and located on genome A and D, respectively.Both 6-SFT-A1 and 6-SFT-A2 were synchronously mapped on chromosome 4A using a DH population (Hanxuan 10 × Lumai 14) and RILs (Yanzhan 1 × Neixiang 188).Total of 14 nucleotide polymorphism sites were identified in 6-SFT-A1, 13 in 6-SFT-A2 and 4 in 6-SFT-D nucleotide sequences.Three haplotypes were detected for 6-SFT-A1 in wheat accessions.Among them, haplotype Ⅰ consist of accessions with medium-drought resistance and drought-sensitive seedling, but haplotype Ⅲ includes the accessions with high-and medium-drought resistance.These two haplotypes of 6-SFT-A1 were also significantly associated with plant height under both drought and well-watered conditions.Three haplotypes of 6-SFT-A2 and two haplotypes of 6-SFT-D showed significant effects on thousand grain weight in both DH and natural populations in multiple combinations of water regimes and years.Among them, haplotype Ⅲ of 6-SFT-A2 and haplotype Ⅰ of 6-SFT-D are significantly associated with high grain weight.Genotypes simultaneously possess two favorable haplotypes, haplotype Ⅲ of 6-SFT-A2 and haplotype Ⅰ of 6-SFT-D exhibited the highest grain weight.Our results showed a potential approach for improving the drought tolerance and grain yield by pyramiding the favorable haplotypes/alleles of the target gene in wheat.