Background <p>Several studies have demonstrated that the cardiometabolic index (CMI) is associated with multiple health conditions. These include kidney diseases, cardiovascular diseases, stroke, and hypertension. The objective of the present research was to investigate the relationship of CMI with the risk of non-alcoholic fatty liver disease (NAFLD) in a sample of the Iranian population.</p> Methods <p>This cross-sectional study included 3,120 participants from the second phase of the Amol cohort study. Ultrasound scanning was utilized to diagnose the NAFLD. The hepatic steatosis index (HSI), fatty liver index (FLI), and CMI values were calculated using standard equations. Multivariate and univariate logistic regression models were employed to investigate the relationship between CMI and NAFLD, FLI, and HSI.</p> Results <p>In the adjusted model, we found that the likelihood of NAFLD increased in the second and last tertiles of CMI compared to the first tertile (T). For NAFLD the odds ratio (OR) were 1.883 (95% confidence interval (CI): 1.487–3.653) in T₂ and 2.801 (95% CI: 2.149–3.653) in T₃. Similarly, the FLI increased with higher CMI tertiles: T₂- OR = 4.888; 95% CI: 3.018–7.919 and T₃- OR = 41.622; 95% CI: 24.201–71.582). A higher likelihood of HSI was also observed in the last tertile of CMI in comparison to the first tertile (OR = 2.344; 95% CI: 1.637–3.356).</p> Conclusions <p>The current study showed a significant association between CMI and NAFLD, as measured by ultrasound, FLI, and HSI. However, due to the cross-sectional design, causal inference is limited, and further prospective studies are needed to validate these results.</p>