Objective <p>To investigate the feasibility of susceptibility-weighted imaging (SWI) for the diagnosis of different stages of liver fibrosis, and to assess its diagnostic accuracy compared with the serum fibrosis index commonly used in clinical settings.</p> Materials and methods <p>This prospective study included 108 patients and 16 healthy volunteers. All patients underwent MRI with SWI and histopathological evaluation. Liver and bilateral erector spinae signal intensities were measured on SWI to calculate liver-to-muscle signal intensity ratios (SIR). Serological biomarkers were collected to calculate the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4). Histological correlation analysis between the SIR and liver fibrosis/iron deposition was performed using Spearman’s rank correlation analysis. The diagnostic accuracies of SIR, APRI, and FIB-4 for staging liver fibrosis were assessed, and their performances were compared using the DeLong test.</p> Results <p>Receiver operating characteristic (ROC) curve analysis showed good-to-excellent diagnostic performance of SIR for different stages of liver fibrosis. The areas under the curve (AUC) of SIR for the diagnosis of liver fibrosis stages S0 vs S1–S4, S0–S1 vs S2–S4, S0–S2 vs S3–S4, and S0–S3 vs S4 were 0.851, 0.868, 0.872, and 0.931. Delong’s test showed that the SIR outperformed the APRI and FIB-4 in the diagnosis of liver fibrosis S0–S1 vs S2–S4, S0–S2 vs S3–S4, and S0–S3 vs S4 (<i>p</i> = 0.011–0.036).</p> Conclusion <p>SWI-based SIR outperforms the serum indicators APRI and FIB-4 in diagnosing liver fibrosis of S0–S1 vs S2–S4, S0–S2 vs S3–S4, and S0–S3 vs S4.</p> Critical relevance statement <p>SWI-based SIR offers a new perspective on non-invasive diagnostic methods to guide the clinical diagnosis of liver fibrosis, particularly in cases where biopsy is contraindicated or impractical.</p> Key Points <p><UnorderedList Mark="Bullet"> <ItemContent> <p>Searching for a non-invasive method to accurately diagnose stages of liver fibrosis is necessary because of the limitations of histopathological evaluation.</p> </ItemContent> <ItemContent> <p>SWI offers a dependable and non-invasive diagnostic approach for evaluating different stages of liver fibrosis compared to serological biomarkers.</p> </ItemContent> <ItemContent> <p>SWI-based SIR provides a highly accurate, non-invasive alternative to serum biomarkers for detecting advanced liver fibrosis.</p> </ItemContent> </UnorderedList></p> Graphical Abstract <p></p>