Objectives The systemic immune-inflammation index (SII), a novel and systematic inflammatory biomarker that is associated with chronic kidney disease (CKD), has not received much attention. This study aimed to investigate the relationship between SII and CKD in the United States (U.S.) population.Methods Our study ultimately included a nationally representative sample of 10,787 adults who participated in the 2007-2018 National Health and Nutrition Examination Survey. Weighted multivariate logistic regression was used to assess the correlation between SII and CKD, and a restricted cubic spline (RCS) model was subsequently used to explore the non-linear relationship between SII and CKD. Subgroup analyses were performed to further the effects of other covariates on the relationship between SII and CKD.Results Following confounder adjustment, a higher SII was related to the incidence of CKD (OR =1.36; 95% CI, 1.07-1.73; p =0.01), as validated by multivariable logistic regression. The RCS curve revealed a non-linear positive correlation between SII/1000 and CKD incidence (p for non-linear =0.0206). Additionally, subgroup analysis confirmed a stronger correlation for male participants (OR =2.628; 95% CI, 1.829-3.776) than for female participants (OR =1.733; 95% CI, 1.379-2.178) (p for interaction =0.046).Conclusions SII is positively associated with the incidence of CKD among U.S. adults, especially in males. However, further studies are needed to confirm our findings and explore the causal factors that can contribute to the prevention and treatment of CKD.