Cytokine interleukin-6 (IL-6) is thought to play a role in Alzheimer's disease (AD) pathogenesis. To explore the correlation between IL-6 receptor gene and sporadic AD (SAD), a case-control study was conducted in a North Chinese Han population. The IL-6R promoter and the exon 9 that contains the proteolytic cleavage site of IL-6R were screened, resulting in three polymorphisms: -530G/T (novel), -208G/A (rs4845617), and +48867A/C (Asp358Ala and rs8192284). There were 328 SAD cases (mean age 75.5+/-9.1 years; mean onset age 69.9+/-8.6 years) and 305 control subjects having a similar age and sex composition. APOE epsilon4 was expectedly more common among the cases (17.7% vs 5.6%; chi(2)=44.375; P<0.001); IL-6R -530T and +48867C were over-represented among the cases (13.4% vs 8.2% P=0.003; 41.8% vs 32.8% P=0.001; OR=2.7 95% CI 1.6-4.5; OR=2.1 95% CI 1.4-3.1). Haplotype analysis indicated five common haplotypes TGA (OR=1.8), GAC, GGC, GAA, and GGA (OR=0.7), from highest to lowest risk. None of the associations appeared to be modified by APOE epsilon4. We conclude that the -530T allele located in a putative regulatory region and the +48867C allele at the splice site may elevate the risk of SAD among the Han Chinese.