Objective: To investigate the relationship between preoperative hepatitis B virus (HBV) DNA load and perioperative complications in patients with hepatitis B-related hepatocellular carcinoma (HCC). Methods: The clinical data of 374 HCC patients undergoing radical hepatectomy between January 2010 and December 2014 were collected. According to the preoperative HBV-DNA load, patients were divided into low-load group (HBV-DNA load<1.0 E+04 IU/mL) and high-load group (HBV-DNA load≥1.0E+04 IU/mL). The changes in postoperative liver function, occurrence of complications and length of hospitalization between the two groups were compared, and the relations of occurrence of complications with clinicopathologic factors were also analyzed. Results: The serum liver function indexes in both groups showed a general trend of initial increase and then decrease, but the increasing amplitudes and peak values of each index in high-load group were greater than those in low-load group (partial P<0.05).The incidence of postoperative pulmonary infection (18.9% vs. 5.2%) and bile leakage (15.4% vs. 2.3%), as well as overall incidence of postoperative complications (19.9% vs. 10.6%) were increased and hospital stay (13.70 d vs. 10.09 d) was prolonged in high-load group compared with low-load group (all P<0.05). Multivariate analysis identified that the preoperative HBV-DNA load (OR=0.865), Child-Pugh classification (OR=0.731) of liver function and tumor size (OR=0.535) were independent risk factors for occurrence of complications (all P<0.05). Conclusion: HCC patients with high preoperative HBV-DNA load may have an increased incidence of perioperative complications and prolonged postoperative hospital stay, and preoperative HBV-DNA is an independent risk factor for surgical complications.