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The SLITs (SLIT1, SLIT2, and SLIT3) are a family of secreted proteins that mediate positional interactions between cells and their environment during development by signaling through ROBO receptors (ROBO1, ROBO2, ROBO3, and ROBO4). The SLIT/ROBO signaling pathway has been shown to participate in axonal repulsion, axon guidance, and neuronal migration in the nervous system and the formation of the vascular system. However, the role of the SLIT/ROBO pathway has not been thoroughly clarified in tumor development. The SLIT/ROBO pathway can produce both beneficial and detrimental effects in the growth of malignant cells. It has been confirmed that SLIT/ROBO play contradictory roles in tumorigenesis. Here, we discuss the tumor promotion and tumor suppression roles of the SLIT/ROBO pathway in tumor growth, angiogenesis, migration, and the tumor microenvironment. Understanding these roles will help us develop more effective cancer therapies.