<p>This study aimed to identify novel genetic variants associated with hyperuricemia risk across multiple nutrients by assessing significant gene–nutrient interactions using large-scale genome-wide association study (GWAS) data in the Korean population. A total of 48,007 individuals from the Korean Genome and Epidemiology Study dataset were included in the GWAS. Dietary intake was evaluated using a food frequency questionnaire. To identify genomic loci that interact with specific nutrients influencing hyperuricemia risk, we conducted a GWAS followed by gene–nutrient interaction analyses of genome-wide significant single-nucleotide polymorphisms (SNPs). Two SNPs with significant gene–nutrient interactions for specific nutrients were identified: rs113206751 in the Membrane-Associated Ring-CH-Type Finger 1 (<i>MARCH1</i>) gene and rs9393235 in the Neuroblastoma-Associated Transcript 1 (<i>NBAT1</i>) gene near the prolactin (<i>PRL</i>) gene. Among individuals consuming vitamin A above the dietary reference intake (DRI), carriers of the minor allele (A) at <i>MARCH1</i>-rs113206751 had a higher risk of hyperuricemia than those with the reference allele (-, no insertion) (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.38–1.93, p: 1.01 × 10^− 8, interaction p: 1.22 × 10^− 6). Among individuals consuming potassium above the DRI, carriers of the minor allele (G) at <i>NBAT1</i>/<i>PRL</i>-rs9393235 showed an increased risk of hyperuricemia than those with the reference allele A (OR 3.14, 95% CI 2.09–4.71, p: 3.69 × 10^− 8, interaction p: 1.21 × 10^− 5). These findings suggest potential gene–nutrient interactions between <i>MARCH1</i> and vitamin A, as well as between <i>NBAT1/PRL</i> and potassium, in relation to hyperuricemia risk. However, these findings may have limited generalizability beyond the Korean population studied and require validation in more diverse populations. This study emphasizes genomic-nutritional integration for personalized hyperuricemia management.</p>