Silicosis is an occupational and irreversible interstitial lung disease, which is caused by the inhalation of respirable crystalline silica. Recent studies suggested that the senescence of endothelial cells is implicated in the pathogenesis of lung diseases. However, the role of senescent endothelial cells in silicosis remains poorly understood. By establishing multiple endothelial cell senescence models, and a silica-induced pulmonary fibrosis mouse model, we found that silica-induced endothelial cell senescence was accompanied by the increased expression of Galectin 3 (Gal3, gene name LGALS3). Mechanistically, silica-induced senescent cells synthesized a substantial amount of Gal3, which was subsequently released into the cellular microenvironment. Then, Gal3 directly binds to TGFBR1 on the cell membrane of lung fibroblasts and TLR4 on the macrophages, respectively. This cell communication facilitates the progression of silicosis by promoting fibroblast-myofibroblast transition (FMT) and NLRP3 inflammasome activation. Furthermore, Gal3 is regulated by the transcriptional regulatory factor CEBPB (CCAAT/ enhancer-binding protein beta) in senescent endothelial cells. In vivo, the administration of Lgals3 siRNA-loaded liposomes significantly ameliorated silica-induced pulmonary fibrosis. Collectively, our study demonstrated the critical role of endothelial cell senescence through the secretion of Gal3, which contributes to pulmonary fibrosis by promoting endothelial-fibroblast and endothelial-macrophage crosstalk.