In conclusion, our study demonstrates for the first time that TM4SF1 can promote laminin-mediated migratory and metastatic ability by interacting with integrin α6 via FAK/PI3K/AKT signaling, which provides new insights into the mechanistic roles of TM4SF1 in ESCC. This evidence concerns the gene TM4SF1 and esophageal squamous cell carcinoma.