Abstract: Metastasis is the main reason leading to the death of cancer patients. Previous studies have found that tumors can establish a pre-metastatic niche in the target organ before metastasis, which provides a supportive and suitable microenvironment for metastasizing cells to colonize. The formation of the pre-metastatic niche involves signal transmission and response. The primary tumor releases signal molecules, which directly or indirectly cause changes in biological behavior of cells of the targeted organ, thus leading to cells secretion of adhesion factors, inflammatory factors and matrix metalloproteinases, etc., and finally forming the niche that facilitates colonization of metastatic cells. This review outlines the establishment process of pre-metastatic niche in the view of cellular transformation response to signal molecules, with particular focus on the transformation process and mechanisms of myeloid-derived suppressor cells, neutrophils, macrophages, resident cells and stromal cells, and further exploration of the application value of this cell transformation process in the development of anti-metastatic drugs.