PDCD5 is a novel apoptosis-related gene. Overexpression of PDCD5 facilitates apoptosis in various tumor cells. Here, we investigated the roles of recombinant human PDCD5 (rhPDCD5) protein in chemosensitivities of hematologic malignancies. The rhPDCD5 increased the in vitro cytotoxicity of daunorubicin (DNR), adriamycin (ADM) and As2O3 in three hematologic tumor cell lines. In vivo studies showed that DNR combined with rhPDCD5 significantly suppressed tumor growth of U937 xenograft nude mice compared with DNR alone. In conclusion, rhPDCD5 combined with the chemotherapeutic drug has greater efficacy than chemotherapy alone, and rhPDCD5 is a very promising chemosensitizer. Overexpression of PDCD5 facilitates apoptosis in various tumor cells. Here, we investigated the roles of recombinant human PDCD5 (rhPDCD5) protein in chemosensitivities of hematologic malignancies. The rhPDCD5 increased the in vitro cytotoxicity of daunorubicin (DNR ), in vivo studies showed that DNR combined with rhPDCD5 significantly suppressed tumor growth of U937 xenograft nude mice compared with DNR alone. In conclusion, rhPDCD5 combined with the chemotherapeutic drug has greater efficacy than chemotherapy alone, and rhPDCD5 is a very promising chemosensitizer.