IgA is an important factor in our immune system. There are many diseases associated with it, such as IgA nephropathy, IgA deficiency, and so on. In order to describe the relationship between the genes and the IgA level, we performed a genome-wide association study of serum IgA with 1,999 healthy Chinese men in the first stage and replicated on an independent Chinese sample with 1,496 subjects in the second stage. Association between each SNP with IgA was estimated by multivariate linear regression analysis conditioned on age and smoke. Haplotype analysis for the block around the top SNP was performed. In the first stage, one genomic locus was identified to be significantly associated with IgA. The loci is TNFSF13 (17p13.1; rs3803800; P = 6.26 × 10(-8)). In smoke-specific analysis, rs3803800 was approximately significantly associated with IgA levels in smokers (P = 3.96 × 10(-7)), while no association was observed in nonsmokers (P = 2.28 × 10(-1)). In addition, we performed the haplotype analysis on chromosome 17 with the SNPs around rs3803800. Although the total P value for the haplotype did not acquire significant difference, three haplotypes (TGAG, CACG, and CACA) reached significant (P < 0.05). In conclusion, TNFSF13 could be a susceptible gene which was discovered having relationship with serum IgA level, and smoke might be a factor infecting the IgA level.