To investigate the role of tumor necrosis factor-alpha (TNF-alpha) in preterm labor and gene polymorphisms of TNF-alpha in genetic susceptibility to preterm labor. We collected maternal serum and partial placental tissues from 46 cases of preterm labor(21 cases of infectious proup with chorioamnionitis, 25 cases of noninfectious group without chorioamnionitis), while obtained maternal serum of 50 cases and placental tissues of 20 cases of term labor in contemporary period. TNF-alpha mRNA in placental tissue was tested by RT-PCR, Maternal serum level of TNF-alpha was measured by ELISA. Based on the genotype results of preliminary studies on TNF-alpha promoter -308 site, we analyzed the difference of placental TNF-alpha mRNA, maternal serum levels of TNF-alpha in different genotypes, and the relationship of different genotypes to chorioamnionitis. The levels of maternal serum TNF-alpha and the mRNA expression of placental TNF-alpha in preterm labor with chorioamnionitis were significantly higher than those of preterm labor without chorioamnionitis and term labor (P < 0.05). There was no significant difference between those of term labor and preterm labor without chorioamnionitis (P > 0.05). In patients with preterm labor, the levels of placental TNF-alpha mRNA and serum TNF-alpha were statistically significant higher in GA(AA) than in GG(P < 0.05), and GA(AA) has significant relationship with chorioamnionitis Codds ratio (OR) 4.22, 95% CI 1.197, 14.8963. It suggested that TNF-alpha -308 polymorphism was associated with the genetic susceptibility to preterm labor. TNF-alpha and its gene polymorphism can be a useful marker for early prediction and diagnosis of preterm labor and intrauterine infection, and may be a genomic index of poor prognosis.