Objective:To investigate the effects of tumor burden score (TBS) and post-radiotherapy alpha-fetoprotein (AFP) stabilization time on the prognosis of hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT).Methods:Clinical data of 40 eligible HCC patients complicated with PVTT admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from July 2018 to March 2022 were retrospectively analyzed. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS), AFP response, and post-radiotherapy AFP stabilization time in the entire group were observed. Diagnostic thresholds were determined by the receiver operating characteristic (ROC) curve. Survival analysis was conducted by Kaplan-Meier method, and the differences of survival rate were assessed by log-rank test. Multivariate analysis was performed by Cox proportional risk model.Results:The optimal cut-off value for TBS was 4.27 [area under the ROC curve (AUC)=0.752, P=0.018]. The ORR in the entire group was 35.7%, with a median OS and PFS of 8 and 5 months, respectively. The median AFP stabilization time was 6 months. Univariate analysis showed that a total of 9 factors were associated with OS, including gender, maximum tumor diameter, TBS, China liver cancer staging, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, gamma-glutamyl transferase (GGT), radiation dose, AFP stabilization time, and tumor response. Multivariate analysis showed that TBS>4.27 ( HR=0.195, 95% CI=0.060-0.638, P=0.007), China liver cancer stage Ⅲb staging ( HR=0.328, 95% CI=0.144-0.745, P=0.008), and AFP stabilization time ≤6 months ( HR=10.282, 95% CI=2.304-45.883, P=0.002) were the independent risk factors for OS in HCC patients complicated with PVTT. Conclusion:HCC patients complicated with PVTT who have low TBS and AFP stabilization time after radiotherapy may obtain longer OS, and the combination of TBS and AFP is expected to become a new risk assessment model.