SH2B1 is well-known as an adaptor protein, and deletion of SH2B1 results in severe obesity and both leptin and insulin resistance. Some studies have revealed that SH2B1 is involved in the progression of lung cancer, esophageal cancer, gastric cancer, oropharyngeal cancer, and so on. Biological function experiments have proven that SH2B1 can regulate cellular morphology, motility and adhesion by modifying the actin cytoskeletal reorganization, and it can promote cell mitogenesis, transformation, survival and differentiation via different signal pathways by enhancing the kinase activity of several receptor tyrosine kinases. In addition, SH2B1 is an obesity-related gene, and epidemiological surveys suggest a complex relationship between obesity and cancer. Therefore, what is the relationship between SH2B1 and cancer? Herein, we attempt to provide a mini overview of the roles of SH2B1 in cancer.