Selective inflow occlusion (SIO) maneuver preserved inflow of nontumorous liver and was supposed to protect liver function. This study aims to evaluate whether SIO maneuver is superior to Pringle maneuver in patients undergoing partial hepatectomy with large hepatocellular carcinomas (HCCs). Between January 2008 and May 2012, 656 patients underwent large HCC resections and were divided into 2 groups: intermittent Pringle maneuver (IP) group (n = 336) and SIO group (n = 320). Operative parameters, postoperative laboratory tests, and morbidity and mortality were analyzed. In comparison to the IP maneuver, the SIO maneuver significantly decreased intraoperative blood loss (473 vs 691 mL, P = 0.001) and transfusion rates (11.3% vs 28.6%, P = 0.006). The rate of major complication between the 2 groups was comparable (22.6% vs 18.8%, P = 0.541). Patients with moderate/severe cirrhosis, total bilirubin > 17 μmol/L, or HBV DNA> = 104 copy/mL in SIO group resulted in lower major complication rates. The SIO maneuver is a safe and effective technique for large HCC resections. In patients with moderate/severe cirrhosis, total bilirubin > 17 μmol/L, or HBV DNA> = 104 copy/mL, the SIO technique is preferentially recommended.