ABSTRACT Background: Lupus nephritis (LN) is one of the most dangerous manifestations of systemic lupus erythematosus (SLE). LN is a complex interplay between genetics, immunological, and environmental factors. Objective: Our study aimed to evaluate tumor necrosis factor α-induced protein-3 (TNFAIP3) mRNA expression level as a noninvasive predictive test of LN and to assess its correlations with clinic-pathologic characteristics as well as disease activity of SLE. Subjects and Methods: Among 150 studied subjects; 80 had SLE and 70 were healthy controls. Patients were stratified into LN group (n=35) and the non-LN group (n=45). TNFAIP3 mRNA expression level was measured using a quantitative real-time PCR. Results: TNFAIP3 mRNA expression level was upregulated in the SLE group compared to the control group. While TNFAIP3 mRNA expression level was downregulated in the LN group of SLE patients compared to the non-LN group. Our results show that the lowest values of TNFAIP3 mRNA expression level were in Class V compared to Class IV, Class III, and Class II. According to the current study results, the effectiveness and strength of TNFAIP3 mRNA expression level for differentiating SLE a from the control group we applied ROC curve, the sensitivities and specificities were 96.8% and 83.3%, respectively. Regards discriminating LN among SLE the sensitivities and specificities were 91.7% and 82.2%, respectively. Thus, TNFAIP3 mRNA expression level could be a useful diagnostic test to discriminate between SLE patients in particular LN patients. Conclusion: Non-LN group had statistically significant higher values of TNFAIP3 mRNA expression level compared to LN and control groups. However, the values decreased with more damage to kidney tissues and progression of SLE activity thus, TNFAIP3 mRNA expression level could be used as a genetic marker of LN susceptibility and severity.