Objective Establish an orthotopic and subcutaneous patient-derived xenografts ( PDX) model of hepatocellular carcinoma (HCC) and compare their growth and pathological characteristics. Methods Fresh tumor tissues from HCC patients from Beijing Ditan Hospital were collected, and implanted in NCG immunodeficiency mice liver and subcutaneous tissues. Their cell growth, pathological characteristics, tumor formation rate, and tumor formation time were analyzed carefully. Results This study established orthotopic and subcutaneous PDX model successfully, and both of them were consistent with the primary tumor pathological characteristics. The tumor formation rate were 50% ( 3 / 6) and 20% (3 / 15) in orthotopic and subcutaneous tissues, respectively. The average tumor formation time were 30 and 68 days in the orthotopic PDX model. Conclusions The orthotopic model has a higher tumor formation rate, it provides a new choice for difficult tumor growth. The subcutaneous model were easy to operate and observe. Hence, the two models were choose according to the specific scientific research practice. They provides effective animal models for further exploration of the pathogenesis of HCC and drug screening.