Present case-control study explored the association between five single nucleotide polymorphisms (SNPs) of interleukin-1 (IL-1) gene family (IL1A−889; rs1800587, IL1B−511; rs16944, IL1B+3962; rs1143634, IL1Rpsti 1970; rs2234650 and IL1RAmspa 11,100; rs315952) and SLE. A sample of 103 Iraqi female patients and 113 healthy matched females were investigated. Serological testing revealed that 91.1 and 88.9% of patients were seropositive for anti-nuclear and anti-double-stranded DNA antibodies, respectively, while none of the control females were seropositive. Serum level of C3 (54 vs. 108 mg/dL) and C4 (5 vs. 21 mg/dL) showed a significant decreased median in patients compared to control. Inspecting IL1 gene SNPs demonstrated a significant increased frequency of IL1A−889C allele in patients compared to control (72.8 vs.56.0%, odds ratio = 1.94, 95% confidence interval = 1.30–2.91), while T allele frequency was significantly decreased (27.2 vs.42.0%). For IL1B−511, IL1B+3962, IL1Rpsti 1970 and IL1RAmspa 11,100 SNPs, allele and genotype frequencies showed no significant variation between patients and control. A significant two-locus linkage disequilibrium (LD) was recorded between IL1B−511 and IL1RAmspa 11,100 SNPs in SLE patients only (log of likelihood odds ratio = 5.69, correlation coefficient = 0.241, LD coefficient = 0.517). Five-locus haplotype frequency estimation revealed that CCCTC and CCTCT haplotypes were positively associated with SLE risk. It is concluded that IL1A−889 SNP is associated with susceptibility to SLE, while, IL1B−511, IL1B+3962, IL1Rpsti 1970 and IL1RAmspa 11,100 SNPs may have no influence on SLE risk. Specific allelic combinations (haplotypes) between the five SNPs may also have a susceptibility role in SLE.