The neutrophil to high-density lipoprotein cholesterol ratio (NHR) is an emerging marker of lipid and inflammatory metabolic dysregulation, previously linked to nonalcoholic fatty liver disease (NAFLD) risk in small-scale studies. However, large-scale analyses and investigations into sex-based differences remain limited. This study aims to evaluate the association between NHR and NAFLD risk across different sexes. Using data from NHANES 2017 to 2020, this study included 6354 eligible adults. Subgroup analyses were performed to assess NHR's predictive effect on NAFLD risk across various populations. Multivariable logistic regression and restricted cubic spline (RCS) analyses were employed to explore the NHR-NAFLD association by sex. All analyses incorporated sample weighting to ensure representative findings. NHR was significantly positively associated with NAFLD risk, with prevalence increasing across higher NHR quartiles (25.92%, 34.69%, 50.25%, 61.60%; P < .001). Males exhibited significantly higher NHR levels than females (P < .001). In males, NAFLD prevalence increased with higher NHR scores, whereas it decreased in females, with significant sex differences (P < .001). Multivariable logistic regression revealed that each one-unit increase in NHR was associated with a 37.5% higher risk of NAFLD in males and a 30.1% increase in females. RCS analysis confirmed a nonlinear association in both sexes, with inflection points at approximately 5.6 for males and 6.1 for females, indicating a significant rise in risk beyond these points. Subgroup analysis showed that the predictive effect of NHR was approximately 12% higher in males (OR = 1.40) compared to females (OR = 1.28), with significant interaction effects (P < .001). NHR has predictive value for nonalcoholic fatty liver disease, and the risk of disease in males is slightly higher than in females. NHR, as a marker of lipid and inflammatory metabolism, can be utilized for the early screening and prevention of nonalcoholic fatty liver disease in the future.Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.