*Purpose: Liver transplantation (LT) is an effective option for hepatocellular carcinoma (HCC) and end-stage liver cirrhosis. However, organ shortage and tumor recurrence are the main obstacles limiting its popularization and application in HCC patients. Testing for circulating tumor cells (CTCs) would be a valuable strategy to predict the recurrence and metastasis of HCC after LT. Various CTC methods have different advantages and disadvantages. This study aims to investigate the predictive value of testing for CTCs based on immunofluorescence in situ hybridization of peripheral blood cells in patients with HCC after LT.

*Methods: A total of 35 patients who received testing for CTCs and then underwent LT were enrolled in this study. Negative enrichment and immunofluorescence in situ hybridization (imFISH) methods were introduced to detect CTCs.

*Results: Twenty (57.1%) patients were CTC-positive, and 15 (42.9%) patients were CTC-negative. No significant associations were observed in baseline data between the CTC-positive and CTC-negative groups (all p>0.05). Twelve (34.3%) patients had recurrence after LT within one year. The results showed that tumor recurrence was correlated with CTC results (ꭓ²=5.115, p=0.034). In multivariate analysis, the CTC results (p= 0.046) and tumor size (p= 0.032) were independent factors impacting long-term survival. The 1-year progression-free survival rates of CTC-negative and CTC-positive patients were 86.7% and 50%, respectively (p= 0.037).

*Conclusions: CTCs and tumor size are closely related to the early recurrence of patients with HCC after LT. CTC-positive patients had a worse prognosis after LT than the CTC-negative group.

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