Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. IL-32, a secreted protein, has been reported to be associated with several autoimmune diseases. Our preliminary experiment showed different plasma IL-32 levels than that mentioned in a published report on the same population. In order to elucidate the correlation between IL-32 and SLE, we determined the plasma level and two single nucleotide polymorphisms (SNPs) of IL-32 in 152 patients with SLE and 310 healthy controls and analyzed the relationship based on the clinical parameters. The results showed that plasma IL-32 levels in patients with SLE were markedly lower than that in the healthy controls. In the SLE group, patients with detectable IL-32 presented low serum C3 concentrations. Further studies indicated that the rs28372698 SNP was associated with the susceptibility to SLE. Taken together, our results suggested that IL-32 could possibly be a candidate marker to monitor SLE disease stability and screening in future.