Background To identify the influence of intraoperative blood transfusion (IBT) on the long-term prognosis of patients with hepatocellular carcinoma (HCC) in patients with low/medium alpha-fetoprotein-tumor burden scores (ATSs) and high ATSs. Methods Data from HCC patients (n = 3374) who underwent liver resection between 2014 and 2022 from a multicenter database were reviewed. The impact of IBT on overall survival (OS) and recurrence-free survival (RFS) in the whole cohort, low/medium ATS group, and high ATS group was evaluated via multivariate analyses, respectively. Results Before propensity score matching (PSM), patients who underwent IBT had poorer RFS (5-year RFS: 37.7% vs. 49.6%, p < 0.001) and OS (5-year OS: 52.8% vs. 68.2%, p < 0.001) than those who did not undergo IBT. After PSM, both RFS (5-year RFS: 37.9%, vs. 45.8%, p = 0.207) and OS (5-year OS: 52.5% vs. 59.5%, p = 0.125) were similar between patients who did and did not receive IBT. Multivariate analysis revealed that the IBT was not associated with RFS or OS in the whole cohort or in patients with high ATSs. However, the IBT was independently related to both RFS (HR = 1.407, 95% CI = 1.089-1.818; p = 0.009) and OS (HR = 1.522, 95% CI = 1.114-2.080, p = 0.008) in patients with low/moderate ATSs. Conclusion Our study confirmed that the IBT had different effects on the prognosis of HCC patients with different ATSs after liver resection. The IBT negatively impacts on the prognosis of patients with low/medium ATSs patients, but not those with high ATSs.