The objective of this study is to understand the role of FcgammaRIIB and FcgammaRIIIA gene in susceptibility to systemic lupus erythematosus (SLE), and to examine possible susceptible haplotypes between two genes. A total of 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, were selected according to 1997 criteria of American College of Rheumatology. In addition, 316 family members of these patients were also genotyped. A family-based association study was used to explore the relationship between gene polymorphism and SLE. We studied 13 single-nucleotide polymorphisms (SNPs) encoding non-synonymous substitution in the FcgammaRIIB and FcgammaRIIIA gene (four SNPs in the FcgammaRIIB gene and nine SNPs in the FcgammaRIIIA gene) with respect to genetic susceptibility to SLE. All SNPs were genotyped by restriction fragment length polymorphism method. Among 13 SNPs, univariate (single-marker) family-based association tests showed that variant alleles at only four SNPs (rs10917661 and rs1050501, in exon 2 and exon 5 of FcgammaRIIB gene, rs403016 and rs428888, in exon3 of FcgammaRIIIA gene respectively) were significantly associated with genetic susceptibility to SLE. Furthermore, the haplotype-specific FBATs showed 50Ter-225Thr (34.1%, in FcgammaRIIB gene) and 72Arg-118Asn (40%, in the FcgammaRIIIA gene) haplotype were more frequently transmitted in SLE than other haplotypes (Z = 3.539, P = 0.00042; Z = 2.678, P = 0.007412 respectively). But haplotypes were not found between FcgammaRIIB and FcgammaRIIIA gene Our results suggest that there were meaningful haplotype in FcgammaRIIIA and FcgammaRIIB gene respectively. FcgammaRIIIA and FcgammaRIIB genes in the pathogenesis of SLE may play an independent role in Chinese population.