Some liver transplant recipients may present with persistent hypersplenism post transplant. Persistent thrombocytopenia and leukopenia may put immunosuppressed transplant recipients at a higher risk of serious, even life-threatening bleeding and infection and limit the use of some drugs (such as mycophenolate mofetil) that could reduce white blood cell and platelet counts during the postoperative period. Herein, we report the first case, to the best of our knowledge, of successful simultaneous anatomic subtotal splenectomy during living donor liver transplantation in a 6-year-old girl with biliary atresia, cirrhotic portal hypertension, severe hypersplenism, and massive splenomegaly. The normalization of platelet and leukocyte counts observed in this patient on the third and first day of the transplant were maintained within the reference ranges during the whole follow-up period, with no significant remnant splenic regrowth and occurrence of serious procedure-related complications. Currently at 48 months of follow-up, the patient has remained in good general condition with normal liver allograft function and peripheral blood cell counts. Our case demonstrates that simultaneous anatomic subtotal splenectomy during liver transplantation may be an effective and feasible treatment for the prevention of persistent hypersplenism post transplant, achieving a long-term desired hematological response, in a selective category of pediatric cirrhotic patients with severe hypersplenism and massive splenomegaly.