The term “humanized mouse” refers to the use of a mouse model with human cells, tissues, or organs. Transplantation of human immune cells into immunodeficient mice is an established humanized mouse model of the immune system that effectively simulates characteristics of the human immune system. Indeed, it provides an ideal experimental tool for studying interactions between the immune system and tumors. In this article, we review the construction method , advantages, and disadvantages of different types of humanized mouse models of the immune system, and further illustrate their applications for tumor immunotherapy.