Aim To explore the effects of apolipoprotein AⅠ (ApoAⅠ) and apolipoprotein AⅠ binding protein (AIBP) on THP-1-derived macrophage pyroptosis. Methods The lactate dehydrogenase (LDH) detection kit was used to evaluate cell membrane integrity, Hoechst33342/PI staining was used to observe cell membrane permeability, ELISA was used to detect the levels of inflammatory factors such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), Western blot was used to detect the expression of pyroptosis-related protein nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), gasdermin D (GSDMD), cleaved Caspase-1, IL-1β and IL-18. Results Oxidized low density lipoprotein (ox-LDL) upregulated the expression of NLRP3, GSDMD-N, cleaved Caspase-1, IL-1β and IL-18 in THP-1-derived macrophages in a concentration-dependent manner, and promoted the release of IL-1β, IL-18 and LDH (P＜0.05 or P＜0.01), indicating that ox-LDL induced pyroptosis in THP-1-derived macrophages in a concentration-dependent manner. Co-treatment of macrophages with ApoAⅠand AIBP significantly downregulated the expression of NLRP3, GSDMD-N, cleaved Caspase-1, IL-1β and IL-18, reduced the release of IL-1β, IL-18 and LDH, and inhibited ox-LDL induced pyroptosis (P＜0.05 or P＜0.01). After ATP-binding cassette transporter A1 (ABCA1) siRNA transfection, co-treatment with ApoAⅠ and AIBP had no significant effect on the expression of pyroptosis-related proteins and secretion of inflammatory factors (P＞0.05). Co-treatment of macrophages with ApoAⅠ and AIBP significantly reduced the expression of purinergic 2X7R receptor (P2X7R) on the cell membrane, inhibited P2X7R mediated protein kinase R (PKR) phosphorylation and NLRP3 inflammasome assembly (P＜0.05 or P＜0.01). After P2X7R siRNA transfection, co-treatment with ApoAⅠand AIBP had no significant effect on the expression of pyroptosis-related proteins and secretion of inflammatory factors (P＞0.05). Conclusion ApoAⅠ and AIBP reduce the expression of P2X7R on the cell membrane through ABCA1, inhibiting P2X7R/PKR/NLRP3 mediated macrophage pyroptosis.