Abstract: OBJECTIVE To explore the association of postoperative incision infection in cardiac surgery patients with tumor necrosis factor-α（TNF-α） G308A gene polymorphism. METHODS A total of 600 patients who underwent cardiac surgery in Wuhan Puren Hospital from Jan 2015 to Jan 2022 were recruited as the study subjects and divided into the infection group with 60 cases and the no infection group with 540 cases according to the status of postoperative incision infection. The risk factors for the postoperative incision infection, distribution of pathogens and TNF-α G308A gene polymorphisms were observed. RESULTS Totally 86 strains of pathogens were isolated from the 60 patients with postoperative incision infection, 45 of which were gram-negative bacteria, 26 were gram-positive bacteria, and 15 were fungi. There were significant differences in length of incision, operation duration, intraoperative blood loss volume, prophylactic use of antibiotics, interleukin（IL）-6, IL-10, TNF-α and procalcitonin（PCT） between the two groups of patients（P＜0.05）. There were significant differences in the frequencies of genotypes of TNF-α G308A between the two groups of patients, and the frequency of GG genotype of the infection group was higher than that of the no infection group（P＜0.05）. The result of logistic analysis showed that the length of incision, operation duration, intraoperative blood loss volume, prophylactic use of antibiotics and TNF-α G308A genotype were the risk factors for the postoperative incision infection（P＜0.05）. The areas under curves（AUCs） of IL-6, IL-10, PCT, TNF-α and TNF-α G308A genotype were 0.760, 0.773, 0.735, 0.836 and 0.892, respectively, and there were significant differences（P＜0.05）. CONCLUSION The length of incision, operation duration, intraoperative blood loss volume, prophylactic use of antibiotics, inflammatory reaction and TNF-α G308A genotype are the risk factors for the postoperative incision infection. The gram-negative bacteria are dominant among the pathogens isolated from the patients with postoperative incision infection.