FAT4 functions as a tumor suppressor, and previous findings have demonstrated that FAT4 can inhibit the epithelial-to-mesenchymal transition (EMT) and the proliferation of gastric cancer cells. However, few studies have investigated the role of FAT4 in the development of colorectal cancer (CRC). The current study aimed to detect the role of FAT4 in the invasion, migration, proliferation and autophagy of CRC and elucidate the probable molecular mechanisms through which FAT4 interacts with these processes. Transwell invasion assays, MTT assays, transmission electron microscopy, immunohistochemistry and western blotting were performed to evaluate the migration, invasion, proliferation and autophagy abilities of CRC cells, and the levels of active molecules involved in PI3K/AKT signaling were examined through a western blotting analysis. In addition, the function of FAT4 in vivo was assessed using a tumor xenograft model. FAT4 expression in CRC tissues was weaker than that in nonmalignant tissues and could inhibit cell invasion, migration, and proliferation by promoting autophagy in vitro. Furthermore, the regulatory effects of FAT4 on autophagy and the EMT were partially attributed to the PI3K-AKT signaling pathway. The results in vivo also showed that FAT4 modulated CRC tumorigenesis. FAT4 can regulate the activity of PI3K to promote autophagy and inhibit the EMT in part through the PI3K/AKT/mTOR and PI3K/AKT/GSK-3β signaling pathways.