This study aims to investigate the potential relationships between the systemic immune-inflammation index (SII) and body mass index (BMI), waist circumference, and the prevalence of obesity. A cross-sectional analysis was conducted on 7,645 individuals aged 20 and above from the NHANES 2017-2020. Multivariate linear regression analyses were conducted to evaluate the association of the logarithmically transformed SII (lgSII) with BMI and waist circumference. Additionally, multivariable logistic regression was utilized to explore the relationship between lgSII and the prevalence of obesity. Fitted smoothing curves and threshold-effect analysis were applied to elucidate nonlinear relationships. In the fully adjusted model, a positive relationship was observed between lgSII and BMI, waist circumference, and obesity prevalence (β = 3.13, 95% CI 2.10-4.16; β = 7.81, 95% CI 5.50-10.13; OR = 1.44, 95% CI 1.12-1.86). The variables of gender, age, race, education, marital status, poverty income ratio (PIR), energy intake, sleep disorder, smoking status, and alcohol use did not significantly modify the positive association between lgSII and obesity. However, physical activity appeared to influence the positive correlation between lgSII and obesity. Using a two-segment linear regression model, an inverted U-shaped relationship was observed between lgSII and both BMI and waist circumference. Furthermore, lgSII demonstrated a linear positive correlation with obesity prevalence. When stratified by physical activity, lgSII showed a non-significant negative correlation with obesity in the physically active group. Our findings underscore a robust association between the logarithmically transformed SII and BMI, waist circumference, and the prevalence of obesity.