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XIST knockdown markedly repressed cell proliferation, migration and invasion and promoted the apoptosis of LSCC cells and the effects were antagonized by loss of miR-125b-5p. MiR-125b-5p was a target of XIST in LSCC cells, and it could bind to TRIB2 as well. Moreover, XIST-loss-induced downregulation of TRIB2 could be significantly reversed by miR-125b-5p knockdown. XIST promoted the growth of LSCC tumor in vivo. CONCLUSION LncRNA XIST promoted the malignance of LSCC cells partly through competitively binding to miR-125b-5p, which in t