Objective: This study investigated the role of long non-coding RNAs (lncRNAs) FTX in vascular endothelial cells (ECs). Methods: Transfection of FTX/Sh-FTX with lentivirus was used to construct gain and loss of function cell models in human umbilical vein endothelial cells (HUVECs). Liquid chromatography-mass spectrometry was used for quantitative proteomics analysis of differentially expressed proteins (DEPs). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein interaction analysis were further conducted to investigate the key molecules and pathways that respond to lncRNA-FTX. Results: In the proteomics analysis, 3308 quantifiable proteins were identified, 64 proteins were upregulated and 103 were downregulated when lncRNA FTX was overexpressed. Additionally, 100 proteins were upregulated and 147 were downregulated when lncRNA FTX was knocked down. Functional clustering analysis of DEPs demonstrated that lncRNA FTX was involved in multiple biological processes. Among them, the expression of complement 3 (C3), cartilage oligomeric matrix protein (COMP), faciogenital dysplasia 6 (FGD6), and tissue inhibitor of metalloproteinase 1 (TIMP1) was significantly upregulated when lncRNA FTX was knocked down, and significantly downregulated when lncRNA FTX was overexpressed. They are associated with inflammation, collagen deposition, angiogenesis, and regulation of liver stem cell differentiation, which may be associated with the occurrence and development of liver fibrosis. Conclusions: The study demonstrated that lncRNA FTX might play a potential role in ECs and contribute to the development of liver fibrosis. Thus, FTX may be a promising target for the prevention or reversal of liver fibrosis.