Objective To investigate whether Ki-67 and DNA topoisomerase Ⅱ α (Topo Ⅱ α) are effective prognostic markers in patients with primary hepatocellular carcinoma (HCC) after liver transplantation.Methods This retrospective cohort study included 105 patients with HCC who underwent liver transplantation in a single center from 2001 to 2012.The demographic features,clinicopathological data,expressions of Topo I c and Ki-67 as detected by immunohistochemistry.The long-term survival and the potential prognostic factors,together with standard histologic parameters,were analyzed by univariate and multivariate analyses.Results A positive correlation was found between Topo II α and Ki-67 levels in HCC (r ＝ 0.469,P ＜ 0.01).Multivariate analyses showed that Ki-67 was an independent prognostic risk factor of recurrencefree survival (HR ＝ 2.296,P ＜ 0.05).The 5-year overall survival rate was related to tumor size (HR ＝ 1.743,P ＜ 0.05),AFP (HR ＝ 2.291,P ＜ 0.05),histological grade (HR ＝ 0.283,P ＜ 0.01),and high expressions of Ki-67 (HR ＝ 1.977,P ＜ 0.05) and Topo Ⅱ α levels (HR ＝ 1.883,P ＜ 0.05).The KaplanMeier analysis showed that there was a significant difference in the 5-year recurrence-free survival rate (40.4％ vs.57.6％) between patients with high and low expressions of Ki-67,which were significantly lower in the high Topo Ⅱ α expression patients (13.5％ vs.63.8％) (P ＜0.01).The 5-year overall survival rates were significantly lower in the high Ki-67 expression patients (12.7％ vs.61.1％,P ＜0.01) when compared with the low Ki-67 expression patients,which were significantly lower in the high Topo Ⅱ α-and Ki-67 expression patients (10.7％ vs.54.5％,P ＜0.01) than the low Topo Ⅱ α-or Ki-67 patients.Conclusions Ki-67 was associated with recurrence and metastasis in patients with primary hepatic carcinoma after liver transplantation.High expression of both Ki-67 and Topo Ⅱ α were associated with poor prognosis in these patients.