Background Lung cancer is one of the leading causes of cancer-related mortality globally. Early identification of high-risk populations is crucial for improving prognosis. The Systemic Inflammatory Index (SII), as an indicator that comprehensively reflects the body's inflammatory status, has unclear potential mediating factors associated with lung cancer risk and differences among different age groups. This study aims to explore the relationship between Sll and lung cancer risk and analyze the differences among different age groups.<br /> Method This study included 37,780 individuals (NHANES data). By comparing their demographic and health-related characteristics, the relationship between Sll and lung cancer risk was analyzed. A weighted generalized linear model was used to analyze the relationship between Sll and lung cancer risk, adjusting for confounding factors such as gender, race, age, smoking history, alcohol drinking history, and the poverty-income ratio (PIR). Subgroup analyses were further conducted to explore the differences in the relationship between Sll and lung cancer risk among individuals above and below the age of 50. In addition, the non-linear relationship between Sll and lung cancer risk was explored through restricted cubic spline plots and threshold effect analysis, and the mediating effect of the Abdominal Body Shape Index (ABSI) was analyzed.<br /> Result The study found significant differences in age, SII, and ABSI between the two groups. Even after adjusting for confounding factors, Sll was positively correlated with lung cancer risk ( OR = 1.0006 , P = 0.004 ) . Subgroup analysis showed a more significant association between Sll and lung cancer risk in individuals over the age of 50 ( OR = 1.0004 , P = 0.006 ) Restricted cubic spline plots and threshold effect analysis revealed a non-linear relationship between SII and lung cancer risk, with a significant inflection point at an Sll value of 1113.6364. Additionally, ABSI had a stronger mediating effect on the relationship between Sll and lung cancer in individuals over the age of 50 (mediating effect: 14.13%), while no mediating effect was observed in individuals under the age of 50.<br /> Conclusion This study indicates that Sll is positively correlated with lung cancer risk, with a more pronounced association in individuals over the age of 50. The mediating effect of ABSI on the relationship between Sil and lung cancer is stronger in individuals over 50 years old, while no mediating effect is observed in those under 50. The non-linear relationship between Sll and lung cancer risk suggests that in clinical practice, the level of Sll and its changing trend should be considered comprehensively.