Abstract: OBJECTIVE To investigate the relationship between plasminogen activator inhibitor-1（Plasminogen Activator Inhibitor-1, PAI） gene polymorphism and the susceptibility to neonatal sepsis. METHODS 98 cases of neonatal septicemia patients who were treated in the Department of Neonatology of the Affiliated Hospital of Chengde Medical College from Jan 2018 to Dec 2020 were selected as the case group, and 90 cases of healthy term neonates in the Department of Neonatology of the Hospital during the same period were randomly selected as the control group. The pathogenic bacteria of neonatal sepsis were identified by blood culture; The peripheral blood C-reactive protein（CRP）, interleukin-6（IL-6）, blood coagulation function index antithrombin Ⅲ（AT-Ⅲ） at the time of enrollment), D-dimer（DD） and platelet（PLT） levels were detected; Polymerase chain amplification reaction and first-generation sequencing were used to detect the genetic polymorphism of PAI gene rs1799768. RESULTS A total of 84 gram-positive bacteria were detected in 98 neonates with positive blood culture sepsis, accounting for 85.71%, 14 cases of gram-negative bacteria, accounting for 14.29%, and Staphylococcus aureus, Group B Streptococcus and Enterococcus faecalis were the pathogens with the highest detection rate. The genotype frequency of 4 G/5 G locus in the case group was significantly higher than that in the control group（P＜0.05）. There was no significant difference between the two groups of 4 G/4 G, 5 G/5 G genotypes and 4 G, 5 G allele frequencies. There was no significant difference between the 4 G/5 G locus genotype and allele distribution of the PAI gene in newborns with gram-negative bacteria infection and gram-positive bacteria infection with sepsis; The overall comparison of the levels of CRP, IL-6, AT-Ⅲ, DD and PLT of the three groups of PAI-1 gene polymorphisms was significant（P＜0.05）; the levels of CRP, IL-6 and DD in sepsis children with 4 G/5 G genotype were significantly higher than those of the other two groups, while the AT-Ⅲ and PLT levels were significantly lower than the other two groups（P＜0.05）. CONCLUSION The 4 G/5 G genotype at the rs1799768 site of the PAI gene significantly increased the risk of neonatal sepsis, but it had nothing to do with the types of pathogenic infection, and its mechanism might be related to the influence on the fibrinolytic system.