Objective To explore the expression of activation-induced cytidine deaminase (AICDA) in renal tissues of patients with systemic lupus erythematosus (SLE) and its clinical significance. Methods The renal biospy tissues from 73 patients with SLE and 36 patients with primary membranous nephropathy, who underwent biopsy between Mar. 2013 to Jun. 2017 in Central South University Xiangya School of Medicine Affiliated Haikou Hospital, were collected. Immunohistochemical method was used to detect the expression of AICDA in renal tissues. The correlations between the expression level of AICDA and the clinicopathological parameters, including pathological classification, system damage, SLE disease activity index (DAI) score and treatment outcome of SLE patients were analyzed. Results The expression level of AICDA in renal tissues of SLE patients was significantly higher than that of primary membrane nephropathy patients (6.12±2.47 vs 3.33±1.91, P<0.05). There was no significant difference in the expression level of AICDA between the type Ⅲ (5.25±4.06), type Ⅳ (6.88±2.20), type Ⅴ (6.10±1.66), type Ⅲ+Ⅴ (5.75±2.34), and type Ⅳ+Ⅴ(5.72±2.37) lupus nephritis patients (all P>0.05). The expression levels of AICDA were significantly higher in renal tissues of SLE patients with oral ulcer, interstitial pneumonia, nervous system damage, arthritis, blood system damage or serositis than those in the patients without above symptoms (7.02±2.14 vs 4.17±1.97, 7.86±2.39 vs 4.98±1.76, 9.83±1.34 vs 5.39±1.92, 6.88±2.04 vs 2.93±1.21, 7.51±1.81 vs 3.70±1.23, and 7.29±2.33 vs 5.34±2.29; all P<0.01). The SLE disease activity index (SLEDAI) score was positively correlated with the expression level of AICDA (P<0.01). The expression level of AICDA in renal tissues of SLE patients with complete remission was lower than that of the patients without complete remission, but the difference was not statistically significant (5.84±2.39 vs 6.80±2.56, P>0.05). Conclusion AICDA is related to the occurrence and development of SLE, and it is expected to bring new targets for the treatment of SLE.