Aim To observe the changes of Toll-like receptor 4 (TLR4) and tumor necrosis factor-α(TNF-α) in patients with acute coronary syndrome (ACS) and its correlation with the severity of coronary artery disease, and to explore its clinical significance. Methods 60 patients with ACS, 20 patients with stable angina pectoris (SAP) and 20 patients with normal control group were selected according to clinical manifestation, ECG and the results of coronary angiography. The ACS patients included 30 patients with acute myocardial infarction (AMI) and 30 patients with unstable angina pectoris (UAP). The degree of coronary artery lesion was evaluated according to the improved Gensini score. In the control group, coronary artery angiography was performed to exclude coronary artery disease. The levels of TLR4 in peripheral blood of 100 patients were detected by flow cytometry, and the concentration of TNF-α in serum were detected by ELISA. Results The levels of TLR4 and TNF-α in ACS group were significantly higher than those in control group and SAP group (P＜0.01), while TLR4 levels were not significantly different between AMI group and UAP group, SAP group and control group (P＞0.05). The levels of TLR4 and TNF-α in patients with ACS decreased but there were significantly lower than those in SAP group and control group (P＜0.05). There was a positive correlation between the expression of TLR4 and TNF-α in blood and the Gensini score of coronary artery lesion (r＝0.715, P＜0.01; r＝0.333, P＜0.01). Conclusions The level of TLR4 in peripheral blood of patients with ACS significantly increased, and the secretion of TNF-α increased. It was suggested that TLR4 and TNF-α concentrations in peripheral blood of patients with ACS were related to the progression of ACS. The levels of TLR4 and TNF-α in peripheral blood were closely related to the degree of coronary artery disease, and after PCI treatment, the expression of TLR4 and TNF-α decreased significantly. It is suggested that myocardial perfusion therapy may improve the coronary artery inflammation.