Objective To evaluate the efficacy of haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) combined with third-party umbilical cord blood (UCB) infusion in treatment of high-risk lymphoblastic malignancies. Methods The clinical data of 20 patients with high-risk lymphoblastic malignancies who received Haplo-HSCT from April 2012 to April 2015 in Shanghai General Hospital were retrospectively analyzed, which were compared with the data from 15 patients who underwent matched unrelated donor HSCT (MUD-HSCT) or 14 matched sibling donor HSCT (MSD-HSCT) during the same period. The efficacy of Haplo-HSCT combined with UCB infusion in treatment of high-risk lymphoblastic malignancies was evaluated. The preparative regimen mainly consisted of teniposide, cyclophosphamide and total body irradiation (TBI). Graft versus host disease (GVHD) preparative regimen included cyclosporine and a short term of methotrexate. The patients who received Haplo-HSCT combined with UCB infusion and MUD-HSCT were treated with antithymocyte globulin (ATG). Results After the transplantation, one patient in MUD-HSCT group and one in MSD-HSCT group died within 21 days, and other patients were engrafted successfully. The median time of neutrophil engraftment was 13 days (10-18 d), 12 days (9-16 d) and 12 days (9-14 d) in Haplo-HSCT + UCB group, MUD-HSCT group and MSD-HSCT group, respectively; the median time of platelets engraftment was 11 days (9-18 d), 12 days (10-23 d) and 12 days (9-14 d), respectively. There were 10, 3, 3 cases of grade Ⅱ-Ⅳacute GVHD at day 100 in the three groups, respectively, and there were 6, 4, 3 cases of chronic GVHD in the three groups, respectively. The 2-year cumulative incidence of relapse was 40.6%, 66.2% and 26.7%, respectively. The predicted 2-year overall survival rate was 37.9%, 42.9% and 55.4%, respectively. All these data had no significant difference (all P＞ 0.05). Conclusion The efficacy of Haplo-HSCT combined with UCB infusion is similar to that of MUD-HSCT or MSD-HSCT in treatment of high-risk lymphoblastic malignancies, which should be recommended to the patients with high-risk lymphoblastic malignancies and without matched donors.