--- - |2+ Abstract Objective To test the Health Literacy Questionnaire (HLQ) in a sample of men with prostate cancer and examine the components of health literacy that are most strongly associated with mental and physical health‐related quality of life in men with prostate cancer. Method Members (N = 565) of a state‐wide prostate cancer support network in Queensland, Australia (Mage = 71.14, SD = 8.68) completed the HLQ along with the Medical Outcomes Study, 36‐item short‐form health survey (SF‐36). Confirmatory factor analysis was employed to assess the internal structure of the HLQ. The effects (bs) of each of the nine health literacy factors on mental and physical health status were graphed and compared using Fishers exact test for comparing parameter estimates. Results Fit indices including RMSEA (0.069, CI = 0.066‐0.072), CFI (.853), and TLI (.839), alongside item loadings and internal consistency (Cronbach alphas >0.80) for the nine‐factor model, supported the robustness of the HLQ for use in this prostate cancer sample. Health literacy factors reflecting social and health provider support, navigating health systems, finding and understanding health information, and active engagement with providers shared small to moderate associations with mental health status and little to no association with physical health status. Conclusion Findings provide support for the use of the HLQ as a valid and reliable measure of health literacy in men with prostate cancer. Although further research is required to establish causality, interventions that aim to improve skills in connecting and effectively communicating with health care services and providers might lead to better mental health related quality of life for men with prostate cancer. - Psycho-Oncology, Volume 27, Issue 10, Page 2374-2381, October 2018.