Aim To explore the effect of anti-inflammation cytokine interleukin-37 (IL-37) on the expressions of nuclear factor-κB (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) activated by Toll-like receptor-4 (TLR4) in human coronary artery endothelial cells (HCAECs) and its mechanism. Methods After 3-5 generations of HCAECs culture, the experiment was carried out and divided into 3 groups:the control group, the IL-37 interference group and the IL-37 overexpression group. The IL-37 interference sequence was added into the IL-37 interference group and the IL-37 DNA overexpressed plasmid was added to the IL-37 overexpression group by liposome transfection. After incubation of 24 hours, the gene transfection efficiency was detected by real-time fluorescence quantitative PCR to determine the success of transfection. Each group was given TLR4 activator lipopolysaccharide (200 μg/L) for intervention. Western blot was used to detect the expression of ICAM-1 protein after intervention of 24 hours and the expressions of phosphorylated NF-κB protein at 0,0, 120 minutes after intervention. Results The expression of ICAM-1 protein increased after TLR4 activation in the control group. Compared with the control group, the ICAM-1 protein increased significantly after TLR4 activation in the IL-37 interference group (P＜0.05), but did not increase in the IL-37 overexpression group (P＞0.05). Compared with the control group, the expression of NF-κB protein was significantly increased at 0,0 and 120 minutes after TLR4 activation in the IL-37 interference group (P＜0.05), but the expression of phosphorylated NF-κB protein was not significantly elevated in the IL-37 overexpression group (P＞0.05). Conclusion IL-37 can inhibit the increase of inflammatory factor ICAM-1 by TLR4 activation in HCAECs, and its mechanism may be through the inhibition of the degree of NF-κB phosphorylation. The anti-inflammatory effect of IL-37 can prevent atherosclerosis.