ABSTRACTWith a high mortality rate, colon cancer (CC) is the third most common malignant tumor worldwide. The primary causes are thought to be the high invasiveness and migration of CC cells. The functions of Golgi phosphoprotein 3 (GOLPH3), stress‐induced phosphoprotein 1 (STIP1), and the signal transducer and activator of transcription 3 (STAT3) signaling pathway in the invasion and migration of CC cells were examined in this study. We collected the exosomes by high‐speed centrifugation. The expressions of GOLPH3, STIP1, and epithelial‐mesenchymal transition (EMT)‐related proteins in CC tissues, cells, and exosomes were analyzed using Western blotting (WB) experiments. The abilities of CC cell invasion and migration were evaluated by the Transwell assay. The binding relationship between GOLPH3 and STIP1 was validated through Co‐immunoprecipitation (Co‐IP), and their sublocalization in CC cells was determined by immunofluorescence detection under laser confocal microscopy. Immunohistochemistry (IHC) experiments detected the expression levels of each protein in the transplanted tumor mass. Animal experiments confirmed the impact of the GOLPH3/STIP1/STAT3 regulatory axis on CC growth. We found that in CC tissues and cells, GOLPH3 was highly expressed, and silencing GOLPH3 not only greatly reduced CC cell invasion and migration but also prevented EMT. Furthermore, GOLPH3 and STIP1 interacted in CC cells, and the GOLPH3‐STIP1 complex affected the capacity for cell invasion and migration by triggering the STAT3 signaling pathway. Noteworthily, GOLPH3, and STIP1 could also be detected in CC cell exosomes, and the exosomes carried the GOLPH3‐ST1P1 complex to act on CC cells to activate intracellular STAT3 signaling, ultimately affecting the cancer cell migration and invasion. The above molecular regulatory mechanisms have also been validated in mice. In conclusion, the GOLPH3‐STIP1 complex acted on surrounding CC cells through exosomes and activated the STAT3 signaling pathway to stimulate CC cell invasion and migration.