Objective:To investigate the effectiveness of antibiotics in preventing surgical site infection (SSI) after hepatectomy.Methods:The clinical data of patients who underwent hepatic resection at the Department of Biliary and Pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, from Jan 2019 to Dec 2021, were retrospectively analyzed.Results:A total of 509 patients were included in the study. There was no statistically significant difference in the incidence of SSI in the different prophylactic treatment time groups ( P>0.05). Univariate analysis revealed bile leakage, extent of hepatic resection, surgical procedure, level of anesthesia, and duration of surgery as potential risk factors for SSI after hepatic resection ( P<0.05); Multivariate analysis showed that bile leakage, extensive hepatic resection, open surgical approach, grade 3-4 anesthesia level, and operative time longer than 300 minutes might be independent risk factors affecting SSI after hepatectomy ( P<0.05). Conclusion:Prolonging antibiotic prophylaxis for SSI after hepatectomy may be unnecessary.