Aims: To explore the relationship between non-high-density to high-density lipoprotein cholesterol ratio (NHHR) and nephrolithiasis incidence among United State adult men and women. Methods: Data was obtained from the 2007-2018 National Health and Nutrition Examination Survey (NHANES) which examined a non-pregnant cohort, ≥20 years of age, with adequate NHHR index and nephrolithiasis information. We employed subgroup assessment and weighted uni- and multivariate logistic regression models to determine the distinct link between NHHR and nephrolithiasis risk. Results: In all, 30969 subjects were recruited for analysis, with 9.97% nephrolithiasis and 2.92±0.02 mean NHHR value. Nephrolithiasis incidence increased with higher quartiles of NHHR. After fully adjusting the covariates, participants with the largest NHHR quartiles exhibited a 34% (OR: 1.34, 95%CI: 1.04–1.72, P = 0.02) raised nephrolithiasis risk, relative to participants with least NHHR quartiles. Based on the two-piece-wise regression, the breakpoint was NHHR = 3.53, and a positive association was more evident when NHHR < 3.53 (OR = 1.22, 95%CI: 1.08–1.37, P = 0.002). When NHHR ≥ 3.53, the correlation disappeared (P = 0.14). Using subgroup and interaction analysis, we reveled a strong association between NHHR and nephrolithiasis. This association was consistent across different population environments, except for a significant interaction effect of smoking status on NHHR.