Background: Long-term survival after liver transplantation (LT) for hepatocellular carcinoma (HCC) patients remains poor because of tumor recurrence. To improve the prognosis of HCC patients after LT, we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center. Methods: In total, data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for analysis. The patients were divided into the following three groups: Group 1, within the Milan and Hangzhou criteria (n = 51); Group 2, beyond the Milan but within the Hangzhou criteria (n = 36); and Group 3, beyond the Milan and Hangzhou criteria (n = 112). Survival probabilities for the three groups were calculated using multivariate Cox regression analysis. The association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression analysis. Results: Child-Pugh stage C and hepatitis B virus (HBV) infection were independent risk factors for patients with tumor recurrence who did not meet the Milan criteria. The overall survival rates of the 199 patients showed statistically significant differences among the three groups (P < 0.001). Moreover, no significant difference was noted in the survival rate between Group 1 and Group 2 (P > 0.05). Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria (OR = 0.478; 95% CI: 0.308-0.741; P = 0.001). Conclusions: Child-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with LT. The Hangzhou criteria were effective and analogous compared with the Milan criteria. Preventive chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT. (C) 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.