This signature effectively stratifies MASLDpatients, discriminating molecular risk groups associated with progression to HCC.<h4>Conclusion</h4>Integrating transcriptomic, clinical and experimental data suggests the role of miR-26a-5p, along with the MASLD-HCC gene signature (EpCAM, DTNA, and KPNA2), may serve as an early molecular indicator and mechanistic modulator of hepatocarcinogenesis, warranting further functional investigation. This evidence concerns the gene KPNA2 and hepatocellular carcinoma.