To investigate the association between the genetic polymorphism of IL-6 C-572G and susceptibility to spontaneous preterm birth (SPTB). Methods The subjects were from Beijing and the surrounding areas of Beijing. This case-control study enrolled 569 SPTB infants, including 56 extremely preterm (<28 weeks of gestation), 166 very preterm (28-31+6 weeks of gestation) and 347 moderate to late preterm infants (32 to 36+6 weeks of gestation). A total of 673 term infants were enrolled as the control group. The latest Sequenom MassARRAY®SNP detection technique was used for the typing of single nucleotide polymorphism of IL-6 C-572G. Results Compared with the CC genotypes, the IL-6 C-572G G-positive genotype (CG+GG genotype) was significantly associated with an increased susceptibility to moderate to late SPTB (OR=1.35, 95%CI: 1.01-1.80, P=0.04). Conclusions Among the Chinese population, IL-6 C-572G polymorphism is associated with susceptibility to moderate to late SPTB.