Objective: To investigate the relationship between CD154 levels of peripheral blood mononuclear cells and coronary calcification in patients with systemic lupus erythematosus (SLE). Methods: Total of 80 cases of SLE patients and 80 healthy cases were selected as research objects. We used flow cytometry to detect serum CD154 level and used multi spiral CT (MSCT) to detect coronary artery calcium score (CACs). CD154 and CACs of two groups were compared. The correlation between the two groups and the risk factors of coronary artery calcification in SLE patients were analyzed. Results: The CD154 level of single nuclear cells in peripheral blood of SLE patients was significantly higher than that in healthy control group, 26.19% (15.98%–34.18%) and 5.89% (1.34%–8.29%) respectively, and the difference was statistically significant (P<0.05). The CD154 level of single nuclear cells in peripheral blood of CACs >400 scores was significantly higher than that in CACs ≤400 scores, 34.24% (25.98%–39.18%) and 20.21% (16.98%–24.18%) respectively, and the difference was statistically significant (P<0.05). Result of spearman rank correlation analysis showed that the CD154 level in SLE patients was significantly positively correlated with CACs (r=0.504, P<0.05). Result of multivariate progressive regression analysis showed that the factors influencing the severity of CACs in SLE patients included age, course of disease, diabetes and CD154. Conclusion: The CD154 level of individual nuclear cells in patients with SLE was significantly higher than that of normal patients. High levels of CD154 were associated with severe coronary calcification. CD154 may be involved in the development of coronary artery calcification in SLE patients.