Alpha-(1,2)-fucosyltransferase (FUT1) gene has been identified as a candidate gene for regulating the expression of Escherichia coli F18 receptor gene (ECF18R) which promotes adherence of Enterotoxigenic (ETEC) and Verotoxigenic (VTEC) Escherichia coli (E. coli) via F18 fimbriae. In order to illustrate the polymorphisms of FUT1 and their effects on resistance to natural infection by Porcine Respiratory and Reproductive Symdrome Virus (PRRSV) and Haemophilus parasuis, the distributions of different genotypes and the relative risks of disease incidence in pigs were investigated. A total of 1,041 pigs representing three European breeds (Duroc, Landrace and LargeWhite), five Chinese local breeds (Wild pig, Small MeiShan, QinPing, JinHua, and JianLi) and three commercial populations (LargeWhite × JianLi, Duroc × Landrace × LargeWhite and Duroc × wild pig) were selected to analyze the genotype of the FUT1 gene by PCR-RFLP. Only the GG genotype associated with susceptibility to ECF18 bacteria was detected in Chinese local pig breeds and a population of LargeWhite × JianLi, while the AA genotype which confers resistance to ECF18 was detected in two European breeds (Duroc and LargeWhite), two populations of Duroc × wild pig and Duroc × Landrace × LargeWhite. Regarding relative risk of incidence, Duroc × Landrace × LargeWhite with genotypes GG or AG showed greater relative risk (OR = 2.040, P = 0.025; OR = 1.750, P = 0.081, respectively) than those with genotype AA during natural infection by both PRRSV and Haemophilus parasuis. It can be concluded that the mutation of FUT1 gene might play a role in pig infection by multi-pathogens, and that AA may be a favourable genotype for increasing the resistance to disease.