Diarrhoea caused by enterotoxigenic Escherichia coli (ETEC) expressing F4 (F4ab, F4ac and F4ad) fimbriae is a significant cause of mortality and morbidity in newborn and weaned pigs. The locus controlling susceptibility towards ETEC F4ab/ac has been mapped to SSC13q41, in which TFRC (transferrin receptor) was localized and considered as a positional candidate gene for ETEC F4ab/ac receptor. In this study, we determined susceptibility/resistance to ETEC F4ab/ac in a total of 755 F2 animals from a White Duroc x Erhualian intercross using a microscopic enterocyte adhesion assay. We identified two TFRC polymorphisms (SNPs 591 A>G and 632 A>G) in a single exon after comparative sequencing analysis of 2371-bp amplicons containing the complete coding region of TFRC using RNA of eight full-sib F2 animals with susceptible and resistant phenotypes. The intron sequences flanking the two exon polymorphisms were obtained, revealing an intron polymorphism (SNP 291 C>T). We genotyped the 19 founder animals of the White Duroc x Erhualian intercross for the identified polymorphisms, showing that only the 291 C>T polymorphism is a highly informative marker. We further genotyped all 59 F1 and 755 F2 animals for the 291 C>T polymorphism, and the association of this polymorphism with susceptibility/resistance to ETEC F4ab/ac in these F2 animals was evaluated by the transmission disequilibrium test. The result showed that the 291 C>T polymorphism is not a causal mutation, however, has a significant linkage disequilibrium with the ETEC F4ab/ac, especially F4ac receptor locus.