Objective To investigate the impact of hepatectomy combined with splenectomy on hepatitis B virus (HBV) reactivation in patients with hepatocellular carcinoma (HCC) ≤5 cm and with hypersplenism.Methods This is a retrospective case-control study on 167 patients with HCC ≤5 cm and with hypersplenism who underwent hepatectomy combined with splenectomy at the Shengli Oilfield Central Hospital between May 2008 and June 2015.64 patients underwent hepatectomy combined with splenectomy,and 103 patients hepatectomy alone.The patients were assigned to the hepatectomy combined with splenectomy group (the combined group,n =61) or the hepatectomy alone group (the control group,n =61) using propensity score matching (PSM).Logistic regression was used to evaluate the relative clinical factors associated with HBV reactivation.The stratified Chi-squared test was utilized to determine the impact of the surgical procedure and preoperative anti-viral therapy on postoperative hepatitis B virus reactivation of these patients.Results The serum PLT level,Child-Pugh grading,tumor diameter and surgical procedures were shown to be independent risk factors associated with postoperative HBV reactivation (P ＜ 0.05).To study the impact of preoperative anti-viral therapy on postoperative HBV reactivation:-the incidence of HBV reactivation was higher in the control group than in the combined group (19.7％ vs.6.6％,P ＜ 0.05).In the combined group,there was no significant difference between patients who received anti-viral therapy and those who were treatment-naive (5.3％ vs.7.1％,P ＞0.05).In the control group,a higher incidence of HBV reactivation was found in patients with treatment-na(i)ve than in patients who received anti-viral therapy (26.1 ％ vs.0,P ＜ 0.05).For the patients who received anti-viral therapy,there was no significant difference between the combined group and the control group (5.3％ vs.0,P ＞ 0.05).In patients with treatment-na(i)ve,a higher incidence of HBV reactivation was observed in the control group than the combined group (26.1％ vs.7.1％,P ＜ 0.05).Conclusions In patients who were not treated with antiviral therapy,hepatectomy combined with splenectomy decreased the incidence of postoperative HBV reactivation in patient with HCC ≤5 cm and with hypersplenism.For the patients who received preoperative anti-viral therapy,the incidence of postoperative HBV reactivation was not decreased with hepatectomy combined with splenectomy.