A study was conducted to examine the moderating role of physical health quality of life, self-reliance, and emotional control on the association between health locus of control and mental health for 230 men living with prostate cancer. Respondents completed an on-line, self-report questionnaire including (a) a multidimensional measure of health locus of control, (b) a scale assessing mental health, (c) a measure of physical health, (d) a scale assessing self-reliance, and (e) a scale measuring emotional control. Hierarchical regression analyses tested the main and moderating effects of these variables. Results indicated that participants' beliefs in their own capacity to control prostate cancer (i.e., internal locus of control), self-reliance, and emotional control exerted main effects on mental health quality of life. Consistent with prediction, physical health quality of life, self-reliance, and emotional control moderated the association between beliefs that physicians (i.e., doctors locus of control) and family, friends, or peers (i.e., powerful other people locus of control) and mental health. Beliefs that God controls prostate cancer (i.e., God locus of control) were unrelated to mental health. Directions for clinical research and improved, gender-sensitive mental health interventions for men living with prostate cancer are offered.