GLCCI1 variations are found to be associated with response to glucocorticoid therapy in non-Hispanic white subjects with asthma. However, there are also other relevant studies that were not consistent with this finding. In this study we aimed to evaluate the association of GLCCI1 variations with asthma susceptibility and inhaled corticosteroid (ICS) response in a Chinese adult Han population.We genotyped 24 single nucleotide polymorphisms of GLCCI1 in 182 asthmatic patients and 180 healthy controls. Furthermore, we analyzed the association of GLCCI1 variations with ICS response in 30 mild-to-moderate asthmatics.rs11976862 homozygote mutant genotype GG was nominally associated with increased asthma risk (OR = 2.435, 95% CI: 1.221-4.854, p = 0.01148, p(corr) = 0.0127). Recessive model of rs37972, rs37973 and rs11976862 showed that the rare alleles were correlated with less improvement in FEV1 after fluticasone treatment for 12 weeks (p = 0.004, p = 0.009 and p = 0.039, respectively). The GLCCI1 mRNA expression level decreased obviously in asthmatics than in healthy controls (0.037663 ± 0.0216833 vs. 0.046352 ± 0.0235812, p = 0.000). For asthmatics, GLCCI1 mRNA expression level significantly increased after fluticasone treatment for 12 weeks (0.067641 ± 0.031547 vs. 0.030048 ± 0.014613, p = 0.000). Moreover, changes of GLCCI1 mRNA expression were significantly related with rs37973 and rs11976862 in a recessive model (p = 0.014 and p = 0.033, respectively).GLCCI1 variations are associated with asthma susceptibility and ICS response in a Chinese Han adult population. GLCCI1 variations may affect ICS response by modulating GLCCI1 expression.