Objective To investigate the association between the functional polymorphisms of Foxp3 gene and unexplained recurrent spontaneous abortion (URSA).Methods PCR-restriction fragment length polymorphism (rs3761548,rs2294021 ) and PCR with sequence-specific primers (rs2232365,rs5902434) were used to detect four polymorphisms of Foxp3 in 146 URSA cases and 112 normal controls.Results ( 1 ) The frequencies of rs3761548A/C were 10.3％,22.3％ in genotype C/C,38.4％,40.2％ in genotype A/C and 51.4％,37.5％ in genotype A/A between URSA patients and normal controls; the frequencies of rs2232365A/G were 5.5％,15.2％ in genotype A/A,47.9％,50.0％ in genotype A/G,46.6％,34.8％ in genotype G/G between URSA patients and normal controls; they all reached statistical difference ( P＜0.05 ).The carriers of rs3761548A allele and rs2232365G allele increased the risk of URSA (OR=1.73,1.61 ; all P ＜ 0.05 ).(2) There was no difference in the genotypic distribution of rs5902434del/ArTTpolymorphism between cases and controls ( P =0.10),but the frequency of del allele in URSA was statistically increased than that of controls (71.2％,62.5％ ; OR =1.49,P =0.04 ).(3) There was no different distribution in 3 genotypes (C/C,T/C,T/T) and 2 alleles (T and C) of rs2294021T/C between URSA patients and normal controls (P =0.18 and 0.08 ).(4) Estimated haplotype frequency distribution of rs5902434del/ATT,rs3761548A/C and rs22323565A/G showed haplotype del-A-G conferring the susceptibility to URSA ( OR =2.51,P ＜ 0.01 ) but haplotype del-C-G and ATT-A-A could provide protection on URSA ( OR =0.18,0.22 ; all P ＜ 0.01 ).Conclusion Functional polymorphisms of Foxp3 gene could probably confer the susceptibility to URSA,by altering Foxp3 function and (or) its expression.