Objectives The deletion of LCE3C_LCE3B confers susceptibility to psoriasis and rheumatoid arthritis (RA) in Caucasians. The aim of this study was to investigate the variant involvement in RA in the Chinese Han population and to further explore its potential role in the susceptibility to systemic lupus erythematosus (SLE). Methods LCE3C_LCE3B-del was genotyped in 898 patients with RA and 681 healthy controls. Two single nucleotide polymorphisms (SNPs, rs4112788 and rs4085613) in strong linkage disequilibrium with LCE3C_LCE3B-del were then genotyped in patients with RA (n=1222), SLE (n=870) and healthy controls (n=1031). Results The deletion of LCE3C_LCE3B and SNPs rs4112788 and rs4085613 showed an association with RA (allele analysis: p=7.72x10(-4), OR 1.28, 95% CI 1.11 to 1.47; p=6.39x10(-4), OR 1.23, 95% CI 1.09 to 1.38; and p=5.38x10(-4), OR 1.23, 95% CI 1.10 to 1.39, respectively). The two SNPs were also significantly associated with SLE (allele analysis: p=7.68x10(-3), OR 1.19, 95% CI 1.05 to 1.36 and p=5.30x10(-3), OR 1.20, 95% CI 1.06 to 1.37). Conclusions This study provides evidence for an association between LCE3C_LCE3B-del and RA in non-Caucasian populations, and SNPs rs4112788 and rs4085613 tagging LCE3C_LCE3B-del were novel susceptibility factors for SLE.