Predicting resistance or susceptibility to infectious diseases on the basis of the genotypes of animals regarding disease or immune related genes could be important in animal production. We evaluated the potential influence of the genetic polymorphisms of four immune related genes, porcine beta defensin 4, interferon-induced GTP-binding protein Mx1, natural resistance-associated macrophage protein 1 (Nramp1), and Toll-like receptor 2 (TLR2) on post-weaning piglet survivability in farms. We selected a single SNP that satisfied the criteria of non-synonymous substitutions and the minor allele frequency >0.1 from each gene, and performed PCR–RFLP. Distributions of allele and genotype frequencies of the SNPs were, in general, significantly different among the five breeds (Berkshire, Yorkshire, Duroc, Landrace, and Korean native pigs. Initially, 371 randomly collected Yorkshire × Landrace F1 piglets consisting of post-weaning survival (n = 185) and non-survival groups (n = 186) were genotyped for the selected SNPs. For the Nramp1 and TLR2 SNPs, genotype frequencies were significantly different between the two groups (P < 0.05). To confirm the results, additional animals that were collected in a different time-period were genotyped for the Nramp1 (n = 390) and TLR2 (n = 240) SNPs. The results using the combined samples (n = 761) were consistent with the initial analysis (P < 0.01), suggesting that the genetic polymorphisms of Nramp1 and TLR2 affect post-weaning piglet survivability. The relative risks, i.e. odds ratios, between the beneficial and non-beneficial genotypes to piglet survivability were 4.88 and 29.65 for the Nramp1 and TLR2 SNPs, respectively.