To elucidate the role of galectin-3/NLRP3 in atherosclerosis, galectin-3 siRNA transfection in macrophages was conducted, galectin-3 and ApoE dual-deficiency mice were produced, AAV-F4/80-shGalectin-3 was injected, and NLRP3 agonist nigericin was administered.<h4>Results</h4>A substantial content of inflammatory factors, the activation of NLRP3/GSDMD/CASP3/CASP8/RIPK3/pMLKL, and the upregulation of galectin-3 were detected in advanced human and mouse atherosclerotic lesions. Here, CASP8 is linked to atherosclerosis.