Objective: To compare the efficiency of hand-assisted laparoscopic splenectomy (HALS) and open splenectomy (OP) for massive splenomegaly. Methods: The clinical data of patients undergoing splenectomy in our hospital between 2004 and 2010 were retrospectively analyzed to compare the clinical efficacy of HALS and OP in patients with spleen size larger than 20 cm. Results: Forty-one patients with spleen size larger than 20 cm underwent splenectomy, of whom, 21 cases underwent HALS and 20 cases underwent OP. The conversion rate to open surgery of the HALS group was 4.7%. The average blood loss of the HALS and OP group was 227 mL and 887 mL (P=0.01), and blood transfusion was 0 and 0.6 units (P<0.05), respectively. The length of hospital stay of the HALS group was significantly reduced compared with that of the OP group (4.3 days vs. 8.4 days) (P=0.001), and no significant difference was noted in complications between the two groups (P＞0.05). Conclusions: HALS is a safe and effective splenectomy procedure for patients with spleen size larger than 20 cm, and it is a feasible alternative procedure to OP with shorter hospital stay, less blood loss and fewer blood transfusions.