The association between serum ferritin and bone mineral density (BMD) is still controversial. This study aims to investigate the association of serum ferritin level with BMD in US adults.We conducted a cross-sectional study consisting of 8445 participants from National Health and Nutrition Examination Survey. Serum ferritin and lumbar spine BMD were used as independent variables and dependent variables, respectively. We evaluated the association between serum ferritin and lumbar spine BMD through a weighted multivariable linear regression model. Subgroup and interaction analysis was also performed in this study.After adjusting for other confounding factors, serum ferritin was negatively correlated with lumbar spine BMD [β =  - 0.090, 95% CI (- 0.135, - 0.045)]. Further subgroup analysis found that the strongest negative association mainly exists in females aged over 45 years [β =  - 0.169, 95% CI (- 0.259, - 0.079)], and this association is not significant in other groups.The results found that the association between serum ferritin and lumber spine BMD differed by gender and age. Increased level of serum ferritin may indicate a higher risk of osteoporosis or osteopenia in females aged over 45 years.© 2022. The Author(s).