〔Abstract〕 Objective To explore the effects ofSOX4 on the regulation of Wnt, TGF-β and other intracellular and extracellular factors on the proliferation, migration and invasion of lung cancer cells and the possible molecular mechanisms. Methods The pEX-2-SOX4 overexpression plasmid, GFP empty plasmid, shRNA interference plasmid and shNC control plasmid were constructed. The cells were transfected by liposome method, and cell biology experiments were used to verify the effects of overexpression and silencing ofSOX4 gene on cell proliferation, migration and invasion ability and the changes of EMT-related genes in transcription and translation. The transcription level of key factors of EMT-related pathways in the target cells was verified by PCR to speculate on the possible mechanism ofSOX4-mediated EMT on cell proliferation, migration and invasion. Results Cell function experiments confirmed thatSOX4 can promote the proliferation, migration and invasion of lung cancer cells, accompanied by the increase in the expression of EMT positive regulators N-Cad, FN, Vim, Snail, ADAM28 and β-catenin. EMT inhibition was down-regulated by E-Cad expression, but the over expression ofSOX4 in 16 HBE and SK-MES-1 cells mainly showed the up-regulation of EMT inhibitors Smad7, TJP1(ZO-1), TJP2(ZO-2) and WIF1. Whereas in the silent group, the level of factor expression described above was opposite to that of the pEX-2-SOX4 group. Most of these factors directly or indirectly participate in the regulation of lung cancer EMT through Wnt and TGF-β. Conclusion SOX4 can mediate the occurrence of EMT in tumor cells through the signaling pathway represented by Wnt and TGF-β, and promote the proliferation, migration and invasion of lung cancer.