Abstract: OBJECTIVE To investigate the relationship between the polymorphism of Interleukin-27（IL-27） gene and the prognosis of sepsis patients after severe trauma. METHODS A total of 50 patients with severe post-traumatic sepsis admitted to the emergency department of Lu'an Hospital affiliated to Anhui Medical University from May 2019 to May 2020 was selected as the sepsis group, and 60 patients who did not develop sepsis after severe trauma admitted to the hospital during the same period were selected as the sepsis group. SNaPshot technology was used to detect the genotype and allele distribution of IL-27 gene-964 A＞G locus in the peripheral blood DNA of the two groups of patients. The serum lactic acid and IL-27 levels of the two groups of patients were detected, the acute physiology and chronic health score（APACHE II）, sequential organ failure score（SOFA） of patients on admission, and final survival status were counted. RESULTS The frequency of GG genotype and G allele of IL-27 gene-964 A＞G locus in the sepsis group was significantly higher than that of the control group, while the frequency of AA genotype and A allele significantly lower than the control group（P＜0.05）; after adjusting for confounding factors such as gender, age, body mass index, and ISS score at admission, the results of multiple logistic regression analysis showed that the GG gene Type and G alleles of IL-27 gene-964 A＞G locus were independent risk factor for sepsis after severe trauma（P＜0.05）; serum IL-27, blood lactic acid, APACHE II, SOFA scores of severe trauma sepsis patients with type GG were significantly higher than those with AA/AG type（P＜0.05）, and the fatality rate of the severe trauma sepsis patients（58.82%）with GG type was significantly higher than that of patients with AA/AG type（P＜0.05）. CONCLUSION The SNP mutation of IL-27 gene-964 A＞G locus significantly increased the risk of sepsis in patients with severe trauma in this region, and was associated with poor prognosis. Among which, the G allele was susceptible gene, and GG gene was susceptible genotype.