Background/Aim: Treatment of castration-resistant prostate cancer with docetaxel (DOC) often leads to resistance. In this study, we investigated whether manganese (Mn) has the potential to enhance treatment when combined with DOC. Materials and Methods: PC3 cells were exposed to DOC or Mn individually and in combination and cell viability was analysed in a dose- and time-dependent manner. Cell toxicity, cell cycle analysis and apoptotic protein levels were determined after 48 h of treatment. Results: Mn in combination with different concentrations of DOC significantly enhanced the inhibitory effect on cell viability. Although the lowest dose did not cause mitotic arrest, DOC increased toxicity, which was reduced when combined with Mn. Protein analyses indicated that Mn compensates for the suppression of death receptors when combined with a low concentration of DOC and induced non-apoptotic pathways when combined with a higher concentration. Conclusion: Combining DOC and Mn may allow for a reduction in DOC concentration with the potential to reduce side effects.