To study the association of transforming growth factor b1 (TGF-b1) gene single nucleotide polymorphisms (SNPs) and plasma TGF-b1 levels with susceptibility to sepsis. Methods: The genotypes of the TGF-b1 gene rs1800469, rs1800468, rs1800470, and rs1800471 loci in 285 sepsis patients (119 patients with severe sepsis and 166 patients with mild sepsis) and 285 healthy individuals (control group) were analyzed through Sanger sequencing. Enzyme-linked immunosorbent assay was used to detect the levels of plasma inflammatory factors. Results: The TGF-b1 gene SNP rs1800469 C allele was 0.56 times lower than the T allele in terms of risk of susceptibility to sepsis (95% confidence interval [CI]: 0.43-0.72, p < 0.01). Carriers of the A allele at the rs1800468 locus of the TGF-b1 were 2.82 times more susceptible to sepsis than those with the G allele (95% CI: 1.62-4.91, p < 0.01). The T allele at the rs1800470 locus of TGF-b1 produced a lower risk of sepsis than those with the C allele (odds ratio [OR] = 0.74, 95% CI: 0.57-0.94, p = 0.02). The risk of susceptibility to sepsis in the TGF-b1 rs1800471 locus G allele was 3.54 times higher than that of C allele (95% CI: 2.14-5.86, p < 0.01). The TGF-b1 gene rs1800469 T > C and rs1800470 C > T were associated with mild sepsis, whereas rs1800468 G > A and rs1800471 C > G were associated with severe sepsis ( p < 0.01). The TGF-b1 gene rs1800469 T > C and rs1800470 C > T were associated with lower plasma TGF-b1 levels, whereas rs1800468 G > A and rs1800471 C > G were associated with higher TGF-b1 levels ( p < 0.05). Conclusion:The alleles T > C of rs1800469 and C > T of rs1800470 of the TGF-b1 gene were associated with lower plasma TGF-b1 levels and a reduced risk of sepsis susceptibility, whereas the alleles rs1800468 G > A and rs1800471 C > G were associated with higher TGF-b1 levels and risk of susceptibility to sepsis.