Objective: To analyze the association between the triglyceride-glucose (TyG) index and the risk of nephrolithiasis across various demographic and clinical subgroups, aiming to enhance early diagnosis and treatment of nephrolithiasis and promote personalized care in diverse populations. Methods: This cross-sectional study analyzed the medical records of 84 968 adults, stratified into three categories (low, middle, high) according to their TyG index scores. To evaluate the association between the TyG index and nephrolithiasis risk, multivariable Logistic regression models were employed, adjusting for potential confounders. Additionally, piecewise linear regression models were used to investigate the non-linear dynamics of the TyG index's relationship with nephrolithiasis risk. Subgroup analyses were performed to explore variations in the effects of the TyG index across different demographic and clinical populations. Results: Increasing TyG index was associated with a higher risk of nephrolithiasis, rising from 4.36% in the low group to 8.96% in the high group (P < 0.001). In adjusted models, males in the middle and high TyG index categories demonstrated significantly elevated risks of nephrolithiasis, with odds ratios of 1.18 (95%CI: 1.07-1.31, P=0.002) and 1.29 (95%CI: 1.15-1.45, P < 0.001), respectively. Conversely, in females, the association was not statistically significant post-adjustment (OR=0.98, 95%CI: 0.82-1.16, P=0.778). Among males, for each unit increment in the TyG index below the critical threshold of 8.98, there was a notable 40% escalation in the risk of developing nephrolithiasis (OR=1.40, 95%CI: 1.24-1.58, P < 0.001). Surpassing this threshold, the TyG index no longer conferred a significant increase in risk (OR=0.91, 95%CI: 0.78-1.06, P=0.24). Subgroup analyses indicated that this association remained stable regardless of age, BMI, or hypertension status. Conclusion: The TyG index is positively associated with the risk of nephrolithiasis in males, demonstrating a nonlinear dose-response relationship that becomes especially pronounced at certain index levels. This biomarker could potentially serve as a valuable clinical tool for identifying males who are at a high risk of developing nephrolithiasis, thereby enabling targeted preventive strategies. Further research is urgently needed to explore the underlying mechanisms and to verify the applicability of these results across different populations.