The significance of hepatocyte nuclear factors (HNFs) in β-cell development and function has been generally recognized in humans, as evidenced by their associations with cases of maturity onset diabetes of the young (MODY). Common Hepatocyte nuclear factor-1 alpha (HNF1A), Hepatocyte nuclear factor-1 beta (HNF1B) and Hepatocyte nuclear factor-4 alpha (HNF4A) mutations could lead to monogenic forms 3, 5 and 1 of diabetes mellitus, respectively, and were characterized by MODY in humans. In this study, multiple variants were discovered in the porcine HNF1A and HNF4A genes, and one single-nucleotide polymorphism (SNP) was detected in the HNF1B gene. Using the Iowa State University Berkshire × Yorkshire pig resource population, the HNF1A, HNF1B and HNF4A genes were mapped on chromosomes 14, 12 and 17, respectively. The linkage disequilibrium (LD) analyses indicated that most of the HNF1A variants were not in strong LD with each other; however, nearly all of them were highly significantly (P < 0.01) associated with loin muscle area (LMA). The SNPs c.327-19G>T and c.1768+40_23del were significantly (P < 0.05) associated with backfat and total lipid percentage, and the latter was also associated with muscle glycogen metabolism measures. Four major haplotypes were observed and the association analyses suggested that haplotype 3 (-CGCGD-, I indicates Insertion and D indicates Deletion) was favorable for reduced backfat, while haplotype 1 (-CACGI-) was unfavorably associated with backfat and LMA. There was no significant interaction effect on backfat among the SNPs c.327-19G>T, c.1768+40_23del of the HNF1A gene and c.646C>T of the transcription factor-7-like 2 (TCF7L2) gene. These findings suggest that the HNF1A gene has significant effects on both fatness- and meat production-related traits. No significant associations with production traits with the SNPs from the HNF1B and HNF4A genes were observed in the study.