The mesenchymal-epithelial transition factor (c-Met) is really a receptor tyrosine kinase with hepatocyte growth factor (HGF) since it’s only high-affinity ligand. Aberrant activation of c-Met is connected with lots of human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic effectiveness from the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude rodents were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected based on c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or perhaps in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and caused complete regression in rodents bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 days of MSC2156119J treatment, and the amount of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation demonstrated elevated responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterised by low c-Met expression were less responsive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy didn’t improve effectiveness. These bits of information indicate that selective c-Met/HGF inhibition with MSC2156119J is connected with marked regression of c-Met high-expressing tumors, supporting its clinical development being an antitumor strategy to HCC patients with active c-Met signaling.