Epistasis underlying fertility plays an important role in crop breeding. Although a new female sterile mutant in wheat, XND126, has been identified and a major quantitative trait locus (QTL), taf1, for the female sterility has been mapped, the genetic architecture of the female sterility needs to be further addressed. To identify the interaction involving the gene(s) controlling the female sterility, an investigation was carried out for the seed setting ratio in an F2 population derived from the cross between XND126 and Gaocheng 8901. Among 1250 simple sequence repeat (SSR) primer pairs in the whole genome, a total of 21 markers, obtained by recessive class approach, along with other ten tightly linked markers on reference maps in wheat, were used to survey 243 F2 individuals. As a result, 28 markers were mapped into five genetic linkage groups. The performance for female sterility for each F2 individual was evaluated simultaneously at the Urumqi and Huai'an experimental stations in 2006–2007. The two phenotypic datasets along with marker information were jointly analysed in the detection of QTL using penalized maximum likelihood approach. A total of six QTLs, including two main-effect QTLs, three epistatic QTLs and one environmental interaction and accounting for 0·67–24·55% of the total phenotypic variance, were identified. All estimated effects accounted for 53·26% of the total phenotypic variation. The taf1 detected in previous study was also located on the same marker interval on chromosome 2DS. These results enrich our understanding of the genetic basis of the female sterility.