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Hepatocellular carcinoma (HCC) is the 6th most common cancer and 3rd leading cause of cancer-related death worldwide. We know that HCC subtypes exist because clear clinical, radiographic, and histological differences between patients with HCC are observed. In this study we investigated distinct subtypes of HCC using a mouse-human chimeric Patient Derived Xenograft (PDX) approach. We have performed a large effort to implant more than 100 tumors from human HCC patients from Texas. We have established the protocol and the results have taught us that engraftment using a variety of transplantation techniques will result in a 25-30% engraftment efficiency for early stage surgical tumors. We have established eight new human HCC PDX models that will be highly relevant for therapeutic and biological studies. These represent North American HCCs, including some patients with intermediate/advanced stage HCC, which is a unique resource for the field.