Triglyceride-glucose (TyG) index is a substitute index for insulin resistance, and has been reported to be associated with many diseases, such as myocardial infarction, stroke, hypertension, and depression, while its association with osteoporosis has not been reported. Therefore, this study aims to explore the association between TyG index and osteoporosis. This was a cross-sectional study, and data were extracted from the National Health and Nutrition Examination Survey (NHANES). The association between TyG index and osteoporosis was assessed using logistic regression analysis, and results were shown as odds ratio (OR) and 95% confidence intervals (95%CI). Subgroup analysis was also performed based on age, BMI, and diabetes. A total of 4,351 participants were finally included, with 2,149 female and 2,202 male. After adjusting potential confounders, we found that higher level of TyG index was significantly associated with higher odds of osteoporosis in female with BMI > 30 kg/m 2 (