The patient-derived xenograft (PDX) model established by transplanting the patient’s tumor tissue into immunodeficient mice well preserves the biological characteristics of the primary tumor. However, the stroma component of the tumor tissue from patients is gradually replaced by the mouse-derived matrix over time in mice. The conditions in mice lacking an immune system will also change the microenvironment of the tumor, and the heterogeneity of the primary tumor will gradually be lost, thus limiting the application of the PDX model. The above problems can be resolved by a humanized patient-derived xenograft (Hu-PDX), which was established by transplanting human hematopoietic stem cells (HSCs) into immunodeficient mice, in which exposure to low-dose whole-body irradiation causes damage to bone marrow cells, or other method to clean up the bone marrow, forming humanized immune system mice (HISM). Then, the tumor tissues from patients can be transplanted into the HISM. HSCs in the mice can be induced to produce human immune cells. That makes the microenvironment of the tumor grown more similar to that in humans. This model well maintain the molecular heterogeneity of the primary tumor, and provides a good animal model for individualized tumor treatment.