Objective To investigate the influence of liver fat deposition on the quantification of the liver iron overload using fast-kilovolt-peak switching dual-energy CT imaging and material decomposition technique. Methods A total of 20 healthy SD rats were taken to make 18 PVC tube of homogenate of fresh liver tissue. The dextran with concentration of 50, 40, 30, 20, 10 and 0 mg/ml were mixed with rat liver homogenate and triglyceride with three different concentrations (add fat with volume percentage of 60％, 30％, 10％ and to simulate severe, moderate and mild fatty liver respectively). All samples were placed in standard phantom according to the order of iron concentration from high to low and scanned by GE Revolution CT 256 slices scanner in GSI mode with rapid tube voltage switching between 80 and 140 kVp and with tube current 200 mA, 320 mA, 485 mA respectively. The images of iron (fat)-based substance pair were reconstructed and the virtual iron concentration (VIC) value were recorded. The correlation between VIC and the actual liver concentration (LIC) of the three sets of tube currents (200, 320, 485 mA) was analyzed by Spearman correlation analysis and linear regression. Results LIC and VIC were highly positively correlated with the liver iron deposition model under different tube currents (r value was 0.900 to 1.000, P<0.05). The presence of fat will result in the decrease of VIC value. In a certain X-ray energy range and certain liver iron concentration, the higher the fat content, the more liver iron concentration underestimation were happened in VIC. At 200, 320 and 485 mA, the crossing points of linear equations for 30％and 10％fatty liver iron deposition models were located at VIC=12.682, 12.470 and 13.447 mg/cm3, respectively. Conclusions The fast-kilovolt-peak switching dual-energy CT imaging and material decomposition techniques can be used for quantitative evaluation of liver iron with hepatic steatosis. The presence of fat will lead to a decrease in VIC measurement.