Hematogenous metastasis is one of the most important ways for metastasis of tumor cells and this is a complex pathophysiological process. Tumor cells enter the bloodstream and move with the blood circulation, meanwhile interact with leukocyte, platelets via integrins, or directly interact with endothelial cells to cause a series of biological behaviors and promote the metastasis of tumor cells. These activated integrins, collaborating with other molecules (e.g. integrins, selectins, cytokines and chemokines), will induce various signal cascades to mediate tumor cell adhesion and migration, and form a new metastatic foci. Hence, better understanding of hematogenous metastasis process is of great significance for treating malignant metastasis of tumor cells and improving life of tumor patients. In this review, the roles of integrins during hematogenous metastasis of tumor cells and their signal transduction were summarized, and new perspectives for future investigation were also discussed. The elucidation about the mechanism of hematogenous metastasis of tumor cells will help to provide a rational basis for anticancer drug development and drug target discovery.