PurposeThe role of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is not fully understood.MethodsIn this retrospective analysis, we included 316 HCC patients who underwent hepatectomy and preoperative CTC detection. We selected 41 pairs of matched HCC patients with and without PVTT using propensity score matching (PSM) analysis. We compared the preoperative CTC counts in patients from both the full cohort and the PSM model. We also analyzed their associations with disease-free survival (DFS) and overall survival (OS).ResultsBefore and after PSM analysis, the preoperative CTC counts in the HCC with PVTT group were substantially higher than in the HCC without PVTT group. In both the full cohort of patients and the PSM model, patients with CTC >= 2 had significantly shorter OS and DFS than patients with CTC < 2. The outcomes of HCC patients with PVTT could be well differentiated by preoperative CTC levels. HCC patients with CTC >= 2 had noticeably shorter OS (9.9 months vs. 24.6 months, P = 0.0003) and DFS (6.0 months vs. 12.3 months, P = 0.0041) than those with CTC < 2. Moreover, preoperative CTC >= 2 remained an independent predictor in all groups' multivariate analysis.ConclusionWe discovered a link between preoperative CTC counts and the occurrence of PVTT and confirmed the prognostic significance of preoperative CTC in HCC patients with PVTT. These findings suggest that preoperative CTC counts have the potential to assist in identifying patients with HCC and PVTT who may benefit from surgery.