Emerging epidemiological evidence suggests that T2DM may be associated with an increased risk of certain cancers. However, the underlying molecular mechanism linked these two diseases remains largely unknown. SHP2, a non-receptor protein tyrosine phosphatase encoded by pro-oncogene PTPN11, has been reported involved in insulin resistance through PI3K/Akt/mOTR signaling and has also been considered to play a vital role in carcinogenesis via Ras/Erk pathways. Based on our previous studies, we hypothesize that SHP2 may present a key molecule linked both T2DM and cancers through both Ras/Erk and PI3K/AKT/mTOR signaling pathways. We believe that the comprehensive and detailed investigation of SHP2 may provide a new insight into the underlying molecular mechanism linked both T2DM and cancers, thereby facilitating the process to discover novel therapeutic targets to prevent and treat cancers.