Aims: Sofarenib has been used for advanced hepatocellular carcinoma (HCC) over the last decade. However, the efficacy of sorafenib in recurrent HCC after liver transplantation (LT) compared to the non-LT settings has not been elucidated. Moreover, factors affecting sorafenib efficacy in the LT group have not been extensively clarified. Methods: Between 2008 and 2019, a total of 832 HCC patients (790 in the non-LT group and 42 in the LT group) treated with sorafenib were consecutively enrolled in our study. Primary outcome was overall survival (OS) in the non-LT and LT groups. Secondary outcomes were objective response rate (ORR), disease control rate (DCR) and time to progression (TTP). Subgroup analyses according to metastasis, liver function and intrahepatic tumor burden were also examined. Results: Overall, the median follow-up duration was 152.5 days. The LT group had younger age, better Child-Turcotte-Pugh (CTP) scores, smaller intrahepatic tumors and lower AFP levels than those of the non-LT group. The LT group showed significantly better OS (16.8 vs. 7.1 months, P<0.001, respectively) than the non-LT group. Moreover, the LT group had significantly longer TTP, higher ORR and DCR than in the non-LT group. The superior efficacy of sorafenib in the LT versus non-LT groups was corroborated in detailed sub-group analyses stratified by metastasis or CTP class A. However, in patients with small or no intrahepatic tumor, there were no significant differences in OS, TTP, ORR and DCR between the two groups. Conclusions: Sorafenib in transplant patients is more effective and provide better outcomes than in non-transplant patients. Intrahepatic tumor burden as well as underlying hepatic function is a crucial determinant for the effectiveness of sorafenib.