Objective:To evaluate the effects of polymorphisms of Toll－like receptor 4 (TLR4) on asthma severity and asthma－related phenotypes in a Chinese Han population. Methods:Four tagging single nucleotide polymorphisms (SNPs) in TLR4 gene were detected using GenomeLab SNPstream or TaqMans Genotyping in 318 adult asthmatic patients. Peripheral CD4+CD25high regulatory T cells and expression of TLR4 were detected by flow cytometry. Linear regression and Ordinal logistic regression,adjusted for age,gender,smoking status,inhaled corticosteroid treatment and SPT,were applied appropriately. A 2－sided P value < 0.05 was considered significant. Results:The distribution of each genetic variant met the conditions of the Hardy–Weinberg equilibrium (HWE). We found no evidences supporting a significant association between TLR4 SNPs and eosinophil counts,serum hsCRP,total serum IgE levels in asthmatic patients. However,our results revealed that the TT homozygote of rs1927914 was associated with lower FEV1% in asthmatic patients. An evidently positive association was found between the TT genotype of rs1927914,or the GG genotype of rs10983755 and rs1927907,and asthma severity(P = 0.024,0.009,0.013,respectively),which indicated that the C allele of rs1927914,and the A allele of rs10983755 and rs1927907 had a protective effect on asthma severity. Although no significant association between TLR4 SNPs and the CD4+CD25high regulatory T cell counts in peripheral blood from asthmatic patients was found,the expression of TLR4 on the surface of CD4+CD25high regulatory T cells was related to TLR4 SNPs. Conclusion:TLR4 polymorphisms may influence the severity of asthma. It could be clinically useful for gene therapy of asthma.