Malignant tumors are a major disease threatening human health with disability and mortality rates increasing yearly. Protein tyrosine phosphatase 2 (SHP2) of Src homology 2, an important member of the protein tyrosine phosphatase family, has a wide range of functions, and its expression is elevated in a wide range of solid tumors. SHP2 plays an important regulatory role in invasion, metastasis, proliferation, apoptosis, and drug resistance. A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors, but no systematic studies have reported on the role of SHP2 in digestive system tumors. Here, we reviewed the biological functions and clinical significance of SHP2 in seven tumor types of the digestive system, explored its roles and mechanisms in cancer development stages, and summarized the development of SHP2 inhibitors to further search for potential targets for effective early diagnosis and gene therapy, which is of great significance to improvement the cancer patient survival rate.