Exosomes mediate cellular communications in cancer by transmitting active molecules. However, the CAFs-derived molecular determinants that regulate esophageal squamous cell carcinoma (ESCC) metastasis have not been fully characterized. The purpose of this study was to investigate the potential roles of exosomal LINC01410 of ESCC cells. The characteristics of exosomes were identified using transmission electron microscope (TEM), Nanoparticle Tracking Analysis (NTA). The expression of LINC01410 and miR-122-5p was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. The biological roles of LINC01410 in ESCC cells were investigated using transwell assay. Western blot assay was employed to detect protein levels. The potential downstream molecular mechanism of LINC01410 was demonstrated with dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down. CAFs promote the metastasis and epithelial-mesenchymal transition (EMT) of ESCC cells. CAFs exert their roles by transferring exosomes to ESCC cells, leading to a significant increase of LINC01410 level in ESCC cells. Mechanically, LINC01410 secreted by CAFs-Exo could contribute to metastasis and EMT by sponging miR-122-5p and increasing PKM2 level in TE-1 and Eca-109 cells. Additionally, LINC01410/miR-122-5p/PKM2 axis affecting ESCC metastasis and EMT in vitro and in vivo.Copyright © 2022. Published by Elsevier Inc.