INTRODUCTION: This study aimed to investigate the potential association between the fatty liver index (FLI), metabolic dysfunction-associated steatotic liver disease (MASLD), and the risk of kidney stones using large-scale population-based data. METHODS: This study employed a cross-sectional design, utilizing data from the 2007 to 2018 National Health and Nutrition Examination Survey (NHANES) database. A total of 24,342 participants were enrolled in the study, and fatty liver status was assessed by calculating the FLI. MASLD was diagnosed by FLI in conjunction with cardiometabolic criteria. Data on the history of kidney stones were obtained by self-report. We employed logistic regression models to analyze the association between FLI, MASLD, and kidney stone risk and constructed multivariable adjustment models to control for potential confounders. Furthermore, we used restricted cubic spline curve models to investigate the dose-response relationship between FLI and kidney stone risk and conducted subgroup and interaction analyses. RESULTS: The study's results indicate a strong correlation between increasing FLI quartiles and a notable rise in the prevalence of kidney stones. Specifically, the risk of developing kidney stones was 1.68 times higher among participants in the highest FLI quartile compared to those in the lowest. Furthermore, patients with MASLD exhibited a 1.35-fold increased risk of developing kidney stones compared to those with non-MASLD. Subgroup analyses demonstrated that the correlation between MASLD and kidney stone risk was consistent across multiple subgroups. However, a significant interaction was observed in the subgroups of smoking status, physical activity level, and hypertension (interaction p <
0.05). The restricted cubic spline analysis did not yield a statistically significant nonlinear association between FLI and kidney stone risk. However, the study did identify inflection point values for FLI. CONCLUSION: This study demonstrated an association between FLI and MASLD and the risk of kidney stones. This suggests that these conditions may be pivotal risk factors for kidney stones. Further investigation is required to elucidate these associations' underlying mechanisms and develop efficacious interventions to reduce the risk of kidney stones. Also, formulating personalized prevention and treatment strategies for different population subgroups is paramount.