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Hong Kong Liver Cancer (HKLC) staging system was developed for prognostic and treatment evaluation for hepatocellular carcinoma (HCC) but is not externally validated. We aimed to evaluate and compare HKLC system with Barcelona Clínic Liver Cancer (BCLC) staging system. The prognostic performance, discriminatory ability, and efficacy of treatment recommendations were compared between the BCLC and HKLC systems. Significant differences in survival were found across all stages of BCLC and across stages I to IV of HKLC systems (P < 0.01). HKLC system was associated with higher homogeneity in prognostic accuracy. The survival was similar between patients treated according to the HKLC or BCLC system (P = 0.07). However, more patients were treated according to HKLC recommendations than to BCLC recommendations (57% vs. 47%, P < 0.001). In a hypothetical cohort created by random sampling, patients treated according to the HKLC scheme had better survival compared with patients treated according to the BCLC system (P < 0.001).Subgroup analyses between hepatitis B virus (HBV) and hepatitis C virus (HCV)-related HCC were performed. More HCV-related HCC were at earlier BCLC or HKLC stages (both P < 0.001). The HKLC system was more informative with greater homogeneity in predicting survival in both HBV and HCV cohorts. However, HKLC treatment recommendations were associated with better long-term survival only in HBV-related HCC but not in HCV-related HCC (P < 0.001 and P = 0.79, respectively).In conclusion, we provided external validation of the HKLC system. Compared with the BCLC system, the HKLC system has better prognostic accuracy and therapeutic efficacy in the entire cohort and in HBV-related HCC but not in HCV-related HCC. Due to high heterogeneity among patients of various etiologies, staging and treatment strategies tailored to specific HCC etiology are required.