Abstract: Objective：To study the efficacy and safety of en-bloc method of holmium laser enucleation of prostate (HoLEP) by pre-separation of urethral mucosa for benign prostatic hyperplasia (BPH) with medium and lower volume prostate. Methods：The data of patients with BPH who received en-bloc method HoLEP by pre-separation of urethral mucosa at apex of prostate from July 2016 to July 2018 were retrospectively analyzed. The scope of application, advantages, efficacy, and complications of the operations were recorded and evaluated. Results：All 50 cases were successfully operated. The mean operating time was (36.5±12.2) min and the mean resected prostate volume was (29±13.2) g. The postoperative hemoglobin level for the first day was lower than before operation with (119±15.2) g/L (P<0.05). The four weeks postoperative follow-up showed the mean international prostate symptom score(IPSS) was 9.4±3.6, maximum flow rate(Qmax)was (22.5±2.3) mL/s, post void residual(PVR) was (23.4±9.2) mL and quality of life (QOL) score was 2.4±1.4, with statistical differences compared to the preoperative values (P<0.05). Postoperative urinary frequency and urgency occurred in 4 cases (8.0%) and temporary stress incontinence in 3 cases (6.0%). Conclusions：En-bloc method of HoLEP by pre-separation of urethral mucosa is effective and safe with clear anatomical signs, simple operations, specific curative effect, and low complications. It has a certain clinical reference value for operation of BPH with medium and small volume prostate.