The systemic immunity-inflammation index (SII) is a novel inflammatory marker, and aberrant blood lipid levels are linked to inflammation. This study aimed to look at the probable link between SII and hyperlipidemia. The current cross-sectional investigation was carried out among people with complete SII and hyperlipidemia data from the 2015–2020 National Health and Nutrition Examination Survey (NHANES). SII was computed by dividing the platelet count × the neutrophil count/the lymphocyte count. The National Cholesterol Education Program standards were used to define hyperlipidemia. The nonlinear association between SII and hyperlipidemia was described using fitted smoothing curves and threshold effect analyses. A total of 6117 US adults were included in our study. A substantial positive correlation between SII and hyperlipidemia was found [1.03 (1.01, 1.05)] in a multivariate linear regression analysis. Age, sex, body mass index, smoking status, hypertension, and diabetes were not significantly correlated with this positive connection, according to subgroup analysis and interaction testing (p for interaction > 0.05). Additionally, we discovered a non-linear association between SII and hyperlipidemia with an inflection point of 479.15 using a two-segment linear regression model. Our findings suggest a significant association between SII levels and hyperlipidemia. More large-scale prospective studies are needed to investigate the role of SII in hyperlipidemia.