Abstract: SHP2 is a phosphatase encoded by a proto-oncogene, which is involved in the post-dephosphorylation modification of proteins, plays an important role in multiple signaling pathways related to the control of cancer progression, and becomes a potential target for cancer therapy. SHP2 inhibitors are an emerging field of research that have undergone a design thinking shift from catalytic site inhibitors to allosteric site inhibitors, with significantly improved bioavailability and inhibitory activity. Focusing on allosteric inhibitors, the research progress of SHP2 small molecule inhibitors was reviewed, and the structure-activity relationship was analyzed.