Curcumin is a biologically active iron chelator and induces cytotoxicity in a series of cell lines. Whereas anti-human transferrin receptor monoclonal antibody (TfR-mAb), which can specifically recognize the outer segment of TfR and result in iron deprivation of tumor cells, has been proved to synergize the antitumor effect of many chemotherapeutic drugs. Thus the aim of this study was to investigate the apoptosis inducing activity of curcumin alone or in combination with TfR-mAb in castration resistant prostate cancer (CRPC) PC3 cells. Here we demonstrated that curcumin induces apoptosis in PC3 cells, as assessed by flow cytometry, TUNEL assay and caspase activation. Combining curcumin with TfR-mAb, synergizes the apoptotic effect of curcumin. At apoptotic inducing concentration, curcumin evaluates the expression of TfR1 and IRP1, but inhibits AKT phosphorylation in PC3 cells. Furthermore, iron deprivation and AKT phosphorylation inhibition effect of curcumin was enhanced by TfR-mAb. All together, our results suggest that TfR-mAb enhances the apoptosis inducing activity of curcumin in CRPC cells, iron deprivation and AKT phosphorylation inhibition are potential mechanisms.