Combinations of cancer therapy modalities are attracting attention to improve the outcome of treatment, since single modality has not always been sufficiently effective. The aim of this study was to investigate a new strategy of combined application of ZnO nanorods with anticancer drug daunorubicin (DNR) in photodynamic therapy (PDT). Using a simple one-step solid state reaction in air at room temperature, we were able to fabricate ZnO nanorods as the drug carrier of DNR in drug delivery system. The combination of ZnO nanorods with DNR induced the remarkable improvement in the anti-tumor activity, which has been demonstrated by the flow cytometry, MTT assay and nuclear DAPI staining. Furthermore, the possible signaling pathway was explored by immunocytochemistry. It was noted that the notable photodynamic activity of the non-cytotoxic ZnO nanorods could considerably increase cancer cell injury mediated by reactive oxygen species (ROS). For instance, in human hepatocarcinoma cells (SMMC-7721 cells), our observations demonstrated that ZnO nanorods could obviously increase the intracellular concentration of DNR and enhance its potential anti-tumor efficiency, indicating that ZnO nanorods could act as an efficient drug delivery carrier importing DNR into target cancer cells. Furthermore, photodynamic ZnO nanorods loaded chemotherapeutic agent could induce distinguished improvement in anti-tumor activity with UV illumination. These findings revealed that such modality combinations represent a promising approach in cancer therapy. Copyright © 2010 Elsevier Ltd. All rights reserved.