BACKGROUND: Maximum diameter and number are the main parameters of tumor burden in hepatocellular carcinoma (HCC). Tumor burden score (TBS) shows its distinguished ability to stratify patients with HCC undergoing transcatheter arterial chemoembolization (TACE). However, the prognostic accuracy of TBS in HCC undergoing liver resection and its association with the BCLC stage has not been well evaluated. METHODS: A total of 3044 treatment-naïve HCC patients from six independent medical centers undergoing liver resection were retrospectively analyzed. Survival analyses were conducted by plotting Kaplan-Meier curves and the Log rank test. We further investigated whether the tumor burden score was a feasible subclassification criterion across the BCLC stage. Then, we also used TBS to identify HCC patients beyond BCLC criteria who could benefit most from surgical resection. Finally, univariate and multivariate cox analysis was used to determine independent prognostic predictors. RESULTS: About 44.2% (n=1343) of patients had low TBS, 38.8% (n=1182) had intermediate TBS and 17% (n=519) had high TBS. Overall survival (OS) and recurrence-free survival deteriorated incrementally with increasing TBS ( CONCLUSION: Tumor burden score is a feasible and reliable prognostic tool for prognosis prediction and clinical decisions.