Objective: To investigate the association between the Neutrophil-to-High-Density Lipoprotein Cholesterol Ratio (NHR) and all-cause and cause-specific mortality in the general population using data from the National Health and Nutrition Examination Survey (NHANES). Methods: This prospective cohort study included 38,149 adults from NHANES (1999–2018) with a median follow-up of 112 months. NHR was calculated as the ratio of neutrophil count to HDL-C levels and categorized into quartiles. Kaplan-Meier curves and Cox proportional hazards models were used to assess the relationship between NHR and mortality, adjusting for demographic, lifestyle, and clinical factors. Results: Higher NHR was associated with increased all-cause mortality (HR 1.26, 95% CI 1.04–1.52), cardiovascular mortality (HR 1.38, 95% CI 1.04–1.74), and non-cardiovascular mortality (HR 1.23, 95% CI 1.01–1.50) compared to the lowest quartile. A U-shaped relationship was observed, with inflection points at NHR values of 2.58, 2.14, and 2.58 for all-cause, cardiovascular, and non-cardiovascular mortality, respectively. Conclusion: NHR is an independent predictor of mortality in the general population, highlighting its potential as a simple biomarker for stratifying cardiovascular risk. Future studies should validate these findings in diverse populations and explore the underlying mechanisms.

Neutrophil-to-High-Density Lipoprotein Cholesterol Ratio (NHR), All-Cause Mortality, Cardiovascular Mortality, Non-Cardiovascular Mortality, Inflammation, Dyslipidemia, NHAN