In the present study, findings highlight that autophagy mediated by TRAF6-induced ULK1 ubiquitination played a critical role in CRC metastasis potentiated by SPHK1, providing the SPHK1-TRAF6-ULK1 signaling axis is an underlying novel therapeutic target for CRC. The gene discussed is TRAF6; the disease is colorectal carcinoma.