Partial hepatectomy in mice is a basic model for hepatic research work. Different complications, especially bleeding, bile leakage, and vena cava stenosis, have been observed with the classical technique, which features ligature en-bloc at the base of the hepatic lobes. In order to reduce complications and improve experimental outcome, a novel, rapid, and safe technique was developed, which was characterized by the ligation of the lobar portal triads before the lobes were resected. Compared with previous protocols, the new protocol was associated with much less complications and better survival rates, and can be easily and safely performed without microsurgical equipments and techniques.