Glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC) is often associated with a poor prognosis. GPC3 is a promising target for tumor-specific immunotherapy in HCC. We investigated the diagnostic performance of viscoelastic properties quantified by tomoelastography, a multifrequency MR-elastography (MRE) technique, for the detection of GPC3-positive HCC. Preliminary results showed that reduced stiffness quantified by tomoelastography is a mechanical signature of positive GPC3 expression in HCC. Combining stiffness and serum alpha-fetoprotein (AFP) level could be considered as a viable biomarker for detecting GPC3-positive HCC as well as for predicting the outcome of GPC3-targeted immunotherapy.