Mechanistically, galectin-3 activated the TLR4/MyD88/NF-κB/NLRP3 axis and induced pyroptosis, apoptosis and necroptosis in macrophages.<h4>Conclusions</h4>Macrophage-derived galectin-3 contributed to pyroptosis, apoptosis and necroptosis in concert, promoted vascular inflammation and atherosclerosis through the upregulation of TLR4/MyD88/NF-κB/NLRP3 pathway.<h4>Key points</h4>Pyroptosis, apoptosis, and necroptosis of macrophages occur concurrently in atherosclerosis. Here, TLR4 is linked to atherosclerosis.