The relationship between systemic inflammation and hearing loss (HL) remains unclear. To investigate the association between the systemic immune-inflammation index (SII) and objective HL, this study was performed. Participants from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018 were analyzed. Two types of hearing loss were investigated: speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL). The SII score was constructed using the levels of peripheral neutrophil (N), lymphocyte (L), and platelet (P), and was defined as P multiplied by N/L (in units of 109/L). Weighted multivariable logistic regression and subgroup analysis were used to examine the relationship between HL and high-SII group (≥330 × 109/L). A total of 6428 participants were included in the study. This study found that the high-SII group was positively associated with a higher risk of HL (OR: 1.29, 95% CI: 1.05-1.57, P < .05) and HFHL (OR: 1.24, 95% CI: 1.05-1.46, P < .05), but not significant for SFHL (OR: 1.13, 95% CI: 0.94-1.37, P > .05). Subgroup analysis showed that this association was similar in different age groups. Finally, sensitivity analysis confirmed the robustness of the association. In the full model, increasing SII index per SD was associated with HL (OR: 1.17, 95% CI: 1.09-1.26, P < .001) and HFHL (OR: 1.13, 95% CI: 1.06-1.21, P < .001). The significance of SFHL was not detected with the increasing SII index (OR: 1.13, 95% CI: 0.94-1.37, P > .05). SII score was associated with HL and HFHL in the general adult population of the United States, but was not significantly correlated with SFHL.