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Purpose We aimed to develop and validate a radiomics model for differentiating hepatocellular carcinoma (HCC) from focal nodular hyperplasia (FNH) in non-cirrhotic livers using Gd-DTPA contrast-enhanced magnetic resonance imaging (MRI). Methods We retrospectively enrolled 149 HCC and 75 FNH patients treated between May 2015 and May 2019 at our center. Patients were randomly allocated to a training (n=156) and validation set (n=68). In total, 2260 radiomics features were extracted from the arterial phase and portal venous phase of Gd-DTPA contrast-enhanced MRI. Using Max-Relevance and Min-Redundancy, random forest, least absolute shrinkage, and selection operator algorithm for dimensionality reduction, multivariable logistic regression was used to build the radiomics model. A clinical model and combined model were also established. The diagnostic performance of the models was compared. Results Eight radiomics features were chosen for the radiomics model, and four clinical factors (age, sex, HbsAg, and enhancement pattern) were chosen for the clinical model. A combined model was built using the factors from the previous models. The classification accuracy of the combined model differentiated HCC from FNH in both the training and validation sets (0.956 and 0.941, respectively). The area under the receiver operating characteristic curve of the combined model was significantly better than that of the clinical model for both the training (0.984 vs. 0.937, p=0.002) and validation (0.972 vs. 0.903, p=0.032) sets. Conclusions The combined model provided a non-invasive quantitative method for differentiating HCC from FNH in non-cirrhotic liver with high accuracy. Our model may assist clinicians in the clinical decision-making process.