In the present study, we systematically investigated STC2-mediated early occurrence of EMT and its involvement of colon cancer migration, clinical associations of STC2 level with tumor development stages and CRC patient survival, as well as discovered STC2 functions on CRC tumorigenesis and progression by promoting EMT process through activating ERK/MEK and PI3K/AKT signaling pathways. Here, STC2 is linked to colonic neoplasm.