This cross‐sectional study investigated the interaction between the genetic risk score (GRS) and abnormal high‐density lipoprotein (HDL) cholesterol lipid levels, which are modified by low‐carbohydrate diets (LCDs) and their effects on the prevalence of hypo‐HDL‐cholesterolemia (hypo‐HDL‐C) in Korean adults. Baseline data were obtained from the Ansan and Ansung study of the Korean Genome and Epidemiology Study (KoGES), conducted from 2001 to 2002, that targeted 8,314 Korean adults aged 40–69 years, including old men (47.6%) and women (52.4%), and whole genomic single nucleotide polymorphism (SNP) genotyping was performed. We identified 18 SNPs significantly associated with hypo‐HDL‐C in the proximity of several genes, including LPL, APOA5, LIPC, and CETP, and calculated the GRS. The low‐carbohydrate diet score (LCDS) was calculated on the basis of energy intake information from food frequency questionnaires. Furthermore, we performed multivariable‐adjusted logistic modeling to examine the odds ratio (OR) for hypo‐HDL‐C across tertiles of LCDS and GRS, adjusted for several covariates. Among participants in the highest GRS tertile, those in the highest tertile of the LCDS had a significantly lower risk of hypo‐HDL‐C (OR: 0.759, 95% CI (confidence interval): 0.625–0.923) than those in the lowest tertile of the LCDS. In the joint effect model, the group with the lowest GRS and highest LCDS was found to have the lowest risk of hypo‐HDL‐C prevalence. This study suggests that individuals with a high genetic risk for low HDL concentrations may have a beneficial effect on a lower intake of carbohydrates.