Aim By transfection of small interfering RNA (siRNA) to silence RAW264.7 derived foam cells’ neurite outgrowth inhibitor-B receptor (NgBR) expression, to study the effect of NgBR on reverse cholesterol transport (RCT) of foam cells, explore new methods to prevent atherosclerosis from RCT pathway and provide new ideas for clinical prevention and treatment of coronary heart disease. Methods Using oxidized low density lipoprotein (ox-LDL) to induce the RAW264.7 cells to form foam cells, and using the oil red O staining to identify them. Then the foam cells were divided into 4 groups:blank control group, siRNA negative control group, NgBR-siRNA1 transfection group (siNgBR-1 group) and NgBR-siRNA2 transfection group (siNgBR-2 group). Whereafter siRNA was used to silence NgBR expression in RAW264.7 cells, and the interference efficiency was identified by real-time PCR and Western blot. Then real-time PCR was applied to detect mRNA content of liver X receptor alpha (LXRα), ATP-binding cassette transporter A1 (ABCA1), ATP-binding transporter G1 (ABCG1) in cells of each group, and corresponding protein content of each group cells were detected by Western blot, and the intracellular cholesterol efflux was determined by liquid scintillation counter. Results Ox-LDL induced foam cells formation successfully. Compared with other groups, NgBR mRNA and protein were significantly decreased in siNgBR-1 and siNgBR-2 group (P＜0.05), mRNA and protein expressions of ABCA1, LXRα, and ABCG1 were significantly inhibited (P＜0.05), and the cholesterol efflux was significantly reduced in siNgBR-1 and siNgBR-2 group (P＜0.05). Conclusion NgBR can increase the expression of LXRα and its downstream genes as ABCA1 and ABCG1 related to RCT regulation of macrophage derived foam cells, thereby weaken or avoid the occurrence and development of atherosclerosis, and provide the theoretical basis for clinical prevention and treatment of coronary heart disease.