As secreted protein and membrane-bound proteins, netrins play important roles in biological processes such as neural cell migration, differentiation and apoptosis. Netrins were thought to guide axon outgrowth and central nervous system morphology since they were discovered. Besides, they also participate in physiological processes such as cell adhesion, migration, differentiation, angiogenesis, lymph angiogenesis, and inflammation in non-neural tissues. Recent studies showed that netrins also involved in the regulation of initiation and development of various tumors including colorectal cancer, pancreatic ductal adenocarcinoma. Because of the functional diversity of netrins and the different biological effects of different receptors in tumor tissue, the specific mechanism of their action in tumors remains unclear. Based on current research progress of our group, this review summed up recent research findings on netrins in relation to cancer biology, suggested possible mechanisms, and discussed the implications in cancer research and intervention.