Previous studies have reported comparable oncologic outcome between ABO-incompatible (ABOi) living donor liver transplantation (LDLT) and ABO-compatible (ABOc) LDLT in patients with hepatocellular carcinoma (HCC). We aimed to analyze the relationship between number of therapeutic plasma exchanges (TPE) before LDLT and HCC outcomes in ABOi LDLT. In this single-center retrospective study, 428 adult LDLT recipients with HCC were categorized into three groups according to ABO incompatibility and the number of pretransplant TPE: ABOc (n = 323), ABOi/TPE ≤5 (n = 75), and ABOi/TPE ≥6 (n = 30). The RFS and HCC recurrence rates were compared. Three groups showed similar characteristics in most demographics, pretransplant tumor markers and pathologies. The median initial isoagglutinin (IA) titer was 1:64 (range negative-1:512) in ABOi/TPE ≤5 group and 1:512 (range 1:128-1:4,096) in ABOi/TPE ≥6 group. Five-year RFS was significantly lower (75.7% vs. 72.7% vs. 50.0%, P = 0.005) and HCC recurrence was significantly higher in the ABOi/TPE ≥6 group than in the other groups(16.4% vs. 17.0% vs. 39.4%, P = 0.014). In multivariable Cox regression analysis, ABOi/TPE ≥6 was an independent risk factor for RFS (aHR 1.99, 95% CI:1.02-3.86, P = 0.042) and HCC recurrence (aHR 2.42, 95% CI:1.05-5.57, P = 0.037). More than six pretransplant TPE sessions may increase the risk of HCC recurrence after ABOi LDLT. Reducing TPE sessions to fewer than six should be considered while maintaining immunological stability through IA titer control.