AIM: To investigate the effect of Toll-like receptor 9 (TLR-9) gene rs5743836 (1237 T/C) single nucleotide polymorphism on recurrent infection in patients with diabetic foot (DF). MEHTODS: A total of 128 DF patients admitted to our hospital from June 2020 to June 2022 were collected and divided into an infected group (n=53) and a non-infected group (n=75) according to the presence or absence of recurrent infection. The general data and TLR-9 gene polymorphism were compared between the two groups. The genotypes and allele frequencies of TLR-9 (1237 T/C) gene polymorphism were detected and compared between the two groups. Logistic regression was used to analyze the correlation between TLR-9 gene 1237 T/C polymorphism and recurrence of DF patients. RESULTS: There were significant differences between the two groups in invasive operation, course of antibiotic use and peripheral vascular disease of both lower limbs (P<0.05). The wild type TT homozygote produced two fragments of 108 bp and 27 bp in length, the variant CC homozygote produced three fragments of 60 bp, 48 bp and 27 bp in length, and the heterozygous TC produced four fragments of 108 bp, 60 bp, 48 bp and 27 bp in length. The TLR-9 (1237 T/C) gene identity was 100%. The genotype frequencies met the Hardy-Weinberg genetic equilibrium (P>0.05). There were significant differences in CC gene frequency, TC gene frequency, TT gene frequency, C gene distribution and T gene distribution between the two groups (P<0.05). Logistic regression analysis showed that TLR-9 CC genotype increased the risk of recurrent infection in DF patients in the co-dominant model (OR=5.357, 95%CI: 1.901-15.100). After adjusting for sex, age and smoking (OR=5.341, 95%CI: 1.874-15.015, P<0.01), the C allele significantly increased the risk of recurrent infection in DF patients (OR=2.328, 95%CI: 1.874-15.015, P<0.01). 1.078-5.936), and the difference was statistically significant (P<0.01). The TT genotype and CC+TC genotype of TLR-9 were not significantly associated with smoking history, Wagner grade, peripheral neuropathy, retinopathy, hypertension, osteoporosis and lower extremity arteriosclerosis obliterans in DF patients (P>0.05). There were significant differences in the course of DM, DF, levels of HbAlc, LDL-C, CRP and PCT between patients with CC genotype and patients with TT+TC genotype (P<0.05). CC genotype, DM duration ≥9 years, DF duration ≥5 months, HbAlc<5.00%, LDL-C≥3.03 mmol/L, CRP≥23.25 mg/mL, PCT≥0.87 ng/mL were risk factors for recurrent infection in DF patients (P<0.05). HbAlc, LDL-C, CRP and PCT all showed interaction with TLR-9 (1237 T/C) gene. The risk of recurrent infection in DF patients with abnormal HbAlc, LDL-C, CRP and PCT levels and TLR-9 (1237 T/C) gene polymorphism interaction combination was 2.659 times higher than that in DF patients without the above combination, and the difference was statistically significant (P<0.05). CONCLUSION: CC genotype and C allele of TLR-9　gene 1237 T/C are independent risk factors for recurrent infection in DF patients.