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Background and objectives: Insulin resistance (IR) is frequently associated with chronic low-grade inflammation and has an important role as a mediator in the development of liver disease. Thus, this study aimed to explore the relationship between two indexes of IR and abnormal liver function parameters. Materials and Methods: This cross-sectional study obtained data of 41,510 men and 92,357 women aged ≥30 years from a private health screening institute in Taiwan. Two IR indexes namely triglyceride-glucose (TyG) index and triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio were used to examine their relationship to predict abnormal liver function parameters (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP)). Results: Positive trend was shown for the association of TyG index in the highest quintile (Q5) and risk of high AST (OR = 1.45, 95% CI: 1.33–1.57), high ALT (OR = 1.85, 95% CI: 1.73–1.97), high GGT (OR = 2.04, 95% CI: 1.93–2.15), and high ALP (OR = 1.13, 95% CI: 1.07–1.19) compared with the median quintile (Q3) in the fully adjusted model. Similarly, participants in the Q5 of the TG/HDL-C ratio were associated with 1.38 (95% CI: 1.27–1.49), 1.71 (95% CI: 1.61–1.82), 1.75 (95% CI: 1.66–1.84), and 1.21 (1.16–1.27) odds for having high AST, ALT, GGT, and ALP respectively. The AUC (95% CI) value of the TyG index for predicting high AST, high ALT, and high GGT was 0.699 (0.692–0.705), 0.738 (0.734–0.742), and 0.752 (0.749–0.755), respectively. Meanwhile, the AUC (95% CI) of the TG/HDL-C ratio for predicting high AST, high ALT, and high GGT was 0.680 (0.673–0.686), 0.738 (0.734–0.742), 0.734 (0.731–0.738), respectively. Conclusions: Our study supported that the TyG index and TG/HDL-C ratio may be useful as non-invasive methods to predict the existence of impaired liver function in the early stage. [ABSTRACT FROM AUTHOR]