Background: Plasma lipids have been shown to relate to tumor biology. We aimed to analyze the effect of pre-transplant plasma lipid profiles on post-transplant tumor recurrence in patients with hepatocellular carcinoma and to identify any possible relationship between the pre-transplant lipid profile with maximum tumor diameter, number of tumor nodules, tumor differentiation, portal vein invasion, or serum biomarker levels. Methods: Patients with hepatocellular carcinoma who underwent liver transplants between 2006 and 2021 had data collected prospectively and were analyzed retrospectively. Patients who did not have lipid profile data before transplant and whose post-transplant follow-up period was <90 days were excluded. Patients who had pre-transplant plasma lipid data and whose post-transplant follow-up period was >90 days were included in this study (n = 254). Results: Lower high-density lipoprotein cholesterol levels were found to be significantly associated with post-Tx recurrence (38 vs 29.5, P < .001) and were also significantly associated with macroscopic portal vein thrombosis (39 vs 30.4, P < .021). There was no significant association between plasma lipids and tumor differentiation. Higher high-density lipoprotein cholesterol levels were significantly associated with good overall and disease-free survivals (P = .024 and P = .001). Conclusion: Pre-transplant low plasma high-density lipoprotein cholesterol levels were significantly associated with portal vein thrombosis and poor post-transplant overall and disease-free survivals.