The aim of this study was to explore the interaction between FCRL4 gene and environmental factors in patients with ankylosing spondylitis. Two hundred ninety-seven ankylosing spondylitis (AS) Han Chinese patients were selected who were diagnosed at the Department of Rheumatology, First Affiliated Hospital, Anhui Medical University, in accordance with the modified New York criteria. The single nucleotide polymorphism (SNP) was genotyped by multiplex SNaPshot technique. The interaction between FCRL4 gene and ten environmental factors in AS patients was assessed by using a case-only study. The interaction between FCRL4 gene (rs2777963) and environmental factors was analyzed by chi-square test and logistic models. p values, odds ratio, and 95 % confidence intervals (CIs) were used for estimating the effects of interaction. Odds ratio (OR) for the interaction of gene × environment (G × E) between drinking group and non-drinking group was 2.61 [95 % CI (1.30, 5.23), p=0.007], with statistical significance. Within the cooking oil group, there also may be an interaction of G × E between main animal oil and main plant oil [OR=10.55, 95 % CI (5.55, 20.04), p<0.001]. However, there was no interaction between FCRL4 gene and the other eight environmental factors in patients with AS. The observed significant gene-environment interaction suggests that drinking and cooking oil with FCRL4 gene has a significant interaction. Drinking and cooking oil may be risk exposure factors to take a combined action with predisposing genes in patients with AS. A larger sample case-control study is needed to illustrate the interaction mechanism in the further study.