SHP2 is a promising target for colon cancer immunotherapy.Negative correlation of PTPN11 and STING mediated type I IFN signaling was found in CRC tissues. STING signaling was negatively modulated by SHP2 (encoded by PTPN11) in vitro. SHP2 allosteric inhibitor SHP099 restricted cancer malignant evolution by inducing T cell activation and type I IFN signaling response in a STING-dependent way. This evidence concerns the gene PTPN11 and malignant colon neoplasm.