Ankylosing spondylitis (AS) is a rheumatoid arthritis, which is a common autoimmune disease with a complex genetic etiology. Although HLA-B27 has been identified to be associated with AS, a number of other genes may also be involved in the disease. Fc receptor-like 3 (FCRL3) gene has been shown to be associated with rheumatoid arthritis in Japanese population. Here we aim to explore the association FCRL3 gene and susceptibility to human leukocyte antigen (HLA)-B27-positive AS in Han Chinese population. Among 169 AS patients, the frequencies of C and T (rs7522061) in FCRL3 gene were 38.7 and 61.3%, respectively; in 184 controls (HLA-B27-positive), the frequencies of C and T were 38.6 and 61.4%, respectively. The frequencies of alleles and genotype are not of statistically significant difference in two groups (chi(2) = 0.000, P = 0.983; chi(2) = 0.099, P = 0.952, respectively), but the distribution of HLA-B27 subtypes are statistically significant difference between cases and controls (chi(2) = 8.214, P = 0.042). Our data reveal that the FCRL3 gene does not appear associated with susceptibility to HLA-B27-positive AS in Han Chinese population.