Several humanized mouse models are now being used to study human-specific immune responses and diseases. However, the pivotal needs of fetal tissues for the humanized mice model have been huddled due to the demand for ethical and medical approval. Therefore, we have verified the hematopoietic and immunomodulatory function of HepaRG and developed a new and easy humanized mouse model to replace the use of fetal liver tissue. HepaRG co-transplanted Hu-NSG mice had significantly increased CD45+ lymphocytes and CD19+ B cells and CD3+ T cells than normal Hu-NSG, suggesting enhanced reconstitution of the human immune system. These results have improved the applicability of humanized mice by developing new models that are easily accessible.