Abstract: OBJECTIVE To explore the gene polymorphisms of cytokines in the chronic obstructive pulmonary disease（COPD） patients with pulmonary invasive fungal infection. METHODS Totally 45 patients with secondary pulmonary invasive fungal infection and 65 COPD patients without pulmonary invasive fungal infection who were treated in the Sichuan Forestry Central Hospital from Jun 2018 to Jun 2020 were enrolled in the study and were repectively assigned as the furgal infection group and the antrol group. The genotyping was conducted for the single nucleotide polymorphism（SNP） of interleukin-1β（IL-1β）, interleukin-12（IL-12） and tumor necrosis factor-α（TNF-α） by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）. The genotypes were compared between the two groups of patients, and the influencing factors and etiological characteristics of the secondary pulmonary invasive fungal infection were observed. RESULTS In terms of IL-1β gene at rs1143627 locus, there was no significant difference in the distribution of genotype between the two groups; the frequency of A allele of the fungal infection group was significantly higher than that of the control group（P＜0.05）. In terms of IL-12 gene at rs2243115 and rs3212227 loci, there were significant differences in the distributions of genotypes and allele between the two groups（P＜0.05）. In terms of TNF-α gene at rs1800629 and rs1799724 loci, there was no significant difference in the distribution of genotype between the two groups, however, the frequencies of A allele at rs1800629 locus and rs1799724 locus were significantly higher in the fungal infection group than in the control group（P＜0.05）. Complication with diabetes mellitus, hypoproteinemia and use of antibiotics no less than 7 days were the independent risk factors for the secondary pulmonary invasive fungal infection in the COPD patients（P＜0.05）. CONCLUSION The polymorphisms of IL-1β, IL-12 and TNF-α genes may be associated with the susceptibility to secondary pulmonary invasive fungal infection in the COPD patients, and the risk of infection is also associated with the patient’s own condition and treatment factors. It is necessary for clinicians to take related measures so as to boost the treatment and diagnosis level and improve the prognosis of the patients.