Objective: To investigate the incidence of postoperative incision infection in patients with oral squamous cell carcinoma(OSCC), and to analyze pathogenic bacteria characteristics and infection-related risk factors. Methods: The clinical data of 644 OSCC patients who underwent primary surgery from January 2020 to May 2022 at the Department of Oral and Maxillofacial Surgery in the Affiliated Hospital of Stomatology of Nanjing Medical University were retrospectively analyzed. The distribution of pathogenic bacteria and their antimicrobial susceptibility were studied.Univariate and multivariate stepwise regression analyses were used to analyze the independent risk factors of postoperative incision infection. Results: Among the 644 OSCC patients, 42 cases were infected, with an infection rate of 6.5%. The main pathogens were Pseudomonas aeruginosa(21.4%), Staphylococcus aureus(14.3%) and Enterobacter cloacae (14.3%). The isolated gram-negative bacteria were resistant to penicillins and cephalosporins, and sensitive to sulfonamides and quinolones. The Staphylococcus species in gram-positive cocci were resistant to penicillins and sensitive to vancomycin. Tumor diameter>35 mm, operation time >5 hours, history of diabetes, intraoperative blood transfusion and long-term smoking history were independent risk factors for postoperative incision infection in OSCC patients(P<0.05). Conclusion: OSCC patients have a high rate of postoperative incision infection. Timely pathogens culture should be conducted on patients' incision secretions, which can guide the rational use of antibiotics in clinical practice. Meanwhile, the patients' infectious risk should be evaluated according to their preoperative and operative status, and corresponding preventive measures need to be taken to reduce the incidence of postoperative incision infection, to shorten the recovery time, and to improve patients' quality of life.