To evaluate the association of single-nucleotide polymorphisms (SNPs) in PADI4 mRNA with rheumatoid arthritis (RA) in a Chinese population, we examined the distribution of four exonic SNPs of the PADI4 gene (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C and padi4_104*T/C) and PADI4 gene expression in 70 RA patients and 81 controls. Increased RA susceptibility was associated with the minor alleles of padi4_89 (P = 0.012), padi4_90 (P = 0.002), padi4_104 (P = 0.001) and the functional haplotype carrying the four minor alleles (P = 0.008). Human leukocyte antigen (HLA)-DRB1 shared epitope (SE) alleles were also associated with increased RA susceptibility, and the individuals with minor alleles of four exonic SNPs and SE alleles showed more increased RA susceptibility. The PADI4 expression was significantly higher in RA patients than in controls (P < 0.001). HLA-DRB1 SE alleles and the genotypes carrying the minor alleles of four SNPs were associated with increased PADI4 expression. It is concluded that PADI4 SNPs, functional haplotype and PADI4 expression may contribute to an inherited predisposition to RA in a Chinese population.