CCAAT/enhancer-binding protein β (C/EBP β) has important roles in numerous signaling pathways. The expression of the majority of regulators and target gene products of C/EBP β, including tumor necrosis factor α-induced protein 3 (TNFAIP3) and TNFAIP3-interacting protein 1 (TNIP1), are upregulated in patients with systemic lupus erythematosus (SLE). The aim of the present study was to investigate whether C/EBP β expression is associated with SLE pathogenesis and correlates with TNIP1 and TNFAIP3 expression. Quantitative reverse transcription-polymerase chain reaction analysis was used to assess the expression of C/EBP β, TNIP1, and TNFAIP3 mRNA in peripheral blood mononuclear cells (PBMC) from 20 patients with SLE and 20 healthy controls. Spearman's rank test was used to determine the correlation between C/EBP β expression and SLE disease activity, and that between C/EBP β expression and TNIP1/TNFAIP3 expression in PBMCs from patients with SLE. C/EBP β mRNA expression was markedly increased in patients with SLE compared with healthy controls. The expression of C/EBP β was positively correlated with the SLE disease activity index and negatively correlated with the serum level of complement components C3 and C4. In addition, C/EBP β mRNA expression was increased in PBMCs from SLE patients that were positive for antinuclear, anti-Smith and anti-nRNP antibodies, compared with the antibody negative SLE patients. Furthermore, the mRNA expression levels of C/EBP β in patients with SLE was positively correlated with TNIP1 and TNFAIP3 expression. The results of the current study suggest that the increased expression of C/EBP β in PBMCs and the interaction between C/EBP β and TNIP1/TNFAIP3 may be involved in the pathogenesis of SLE.