BACKGROUNDS AND AIMS: Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer, characterized by a high rate of recurrence. This study aims to compare the efficacy and safety of repeat hepatectomy (RH) and salvage liver transplantation (sLT) for recurrent hepatocellular carcinoma (rHCC) and explores the predictive value of neutrophil-to-lymphocyte ratio (NLR) and neutrophil extracellular traps (NETs). METHODS: In this study, consecutive patients receiving RH (n = 637) or sLT (n = 53) for rHCC within the University of California San Francisco (UCSF) Criteria were recruited. After propensity score matching (PSM), disease-free survival (DFS) and overall survival (OS) were compared utilizing the Kaplan-Meier method. Additionally, the level of neutrophil infiltration and NETs were analyzed by multiplex immunofluorescence. RESULTS: After PSM, the sLT group demonstrated superior 5-year DFS and OS compared to the RH group (p <
0.001 and p = 0.014). Subgroup analysis demonstrated that NLR >
2.3 was associated with poorer OS (p <
0.001 in the RH group and p = 0.024 in the sLT group) and DFS (p = 0.002 in both groups). Furthermore, we identified that patients in the sLT group are more susceptible to extrahepatic metastasis. In addition, our results revealed that higher infiltration of intratumoral neutrophils was negatively correlated with OS and DFS (p = 0.002 and p = 0.001, respectively), especially in cases with higher NETs level. CONCLUSIONS: This study indicates that sLT achieves better long-term outcomes than RH for rHCC. NLR and NETs formation are promising prognostic factors for HCC.