Depression is a major cause of health problems throughout the world. About 300 million people are depressed. The number of people with depression has risen 18% since 2005. Lack mental health service has made people who are depressed are not able to get proper treatment. At the other hand, there is a great strength in the faith to the God. The faith can provide spiritual strength in dealing with life's difficulties. This study aims to determine the effect of the prayer in reducing the level of depression in the Balai Rehabilitasi Sosial Wanita (BPRSW, Social Protection and Rehabilitation Center for Women) Yogyakarta. The research is quantitative research methods and used a purposive sampling technique with 30 respondent. They are assisted residents at the BPRSW Women's Social Protection and Rehabilitation Center. The results of this study shows that the prayer has an effect on reducing the level of high level depression. This is evidenced by the value of the regression coefficient in this study is t -8.484 greater than t table with a significance level of 0.000 less than 0.05 which means that there is an influence of the prayer in reducing the level of depression. Based on the determination coefficient table shows R = 0.720 and R (Square) value of 71.0%. The effect of the prayer method in reducing the level of depression is 71%