4578 Background: Both Portal Vein Embolization (PVE) and Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) have been used in patients with unresectable hepatocellular carcinoma (HCC) due to insufficient volumes in future liver remnant (FLR). But it remains unclear for which thetapy has better long-term overall survival. Methods: This study was a single-center, prospective randomized comparative study. Patients were randomly assigned in a 1:1 ratio to the 2 groups. The primary endpoints was three-year overall survival rates. Results: Between November 2014 to June 2016, 76 patients with unresectable HCC due to inadequate volume of FLR were randomly assigned to ALPPS groups (n = 38) and PVE groups (n = 38). Thirty-seven patients (97.4%) in the ALPPS Group compared with 25 patients (65.8%) in the PVE Group were able to undergo staged hepatectomy (risk ratio 1.48, 95% CI 1.17-1.87, p < 0.001). The three-year overall survival (OS) rate of the ALPPS group (65.8%) (95% CI 50.7-80.9) was significantly better than the PVE Group (42.1%) (95% CI 26.4-57.8), (HR 0.50, 95% CI 0.26-0.98, two-sided p = 0.036). Major postoperative complications rates after the stage-2 hepatectomy were 54.1% in the ALPPS group and 20.0% in the PVE group ((risk ratio 2.70, 95% CI 1.17-6.25, p = 0.007). Conclusions: ALPPS resulted in significantly better long-term overall survival outcomes, at the expenses of a significantly higher perioperative morbidity rate compared with PVE in patients who had initially unresectable HCC. Clinical trial information: ChiCTR-IOC-14005646 .