Objective: To explore the correlation between the severity of coronary artery lesions and serum biomarkers in patients with coronary heart disease(CHD). Methods: A total of 453 patients with CHD were selected as the observation group, while 213 patients without CHD were included as the control group. According to the severity of coronary artery lesions, CHD patients were divided into mild group(n=147), moderate group(n=132)and severe group(n=174). The general information and serum biomarker levels of patients with different severity of coronary artery disease between the observation group and the control group were compared, the correlation between serum biomarker levels and the severity of coronary artery disease were analyzed by Pearson correlation analysis. The influence factors of severity of coronary artery disease in CHD patients were analyzed by Ordered Logistic regression analysis. Results: The comparisons of high-density lipoprotein(HDL), lipoprotein-associated phospholipase A2(Lp-PLA2), D-dimer, B-type natriuretic peptide(BNP), cardiac troponin I(cTnI), fibrinogen(FIB), and C-reactive protein (CRP)in observation group were higher than those in the control group (P <0.05). There were significant differences in the levels of D-dimer, BNP, cTnI, FIB, CRP, and lymphocytes(LYM)among patients with different severity levels of coronary heart disease (P <0.05), with severe group > moderate group > mild group. The correlation analysis results showed that the levels of serum Lp-PLA2, D-dimer, BNP, cTnI, FIB, CRP were correlated with the severity of coronary artery disease in CHD patients (P <0.05). The regression analysis results showed that cTnI and FIB levels were independent risk factors affecting the severity of coronary artery disease in CHD patients(P<0.05). Conclusion: The severity of coronary artery lesions in patients with CHD is associated with the levels of Lp-PLA2, D-dimer, BNP, cTnI, FIB and CRP. Among them, cTnI and FIB are independent risk factors and can assist in clinical assessment.