BACKGROUND: Cancer often progresses very rapidly and either leads to various complications or patients eventually die of the disease. One of important consequences of cancer is depression which can increase the morbidity and mortality in non-treated cases. Religious coping is the use of religious beliefs or practices to reduce distress and deal with problems in life. This study aimed to determine the relationship between religious coping and depression in cancer patients. SUBJECTS AND METHODS: A descriptive-correlational study was conducted on 150 consequent cancer patients in three centers: Imam-Reza Hospital in Birjand, Qaem and Omid hospitals in Mashhad. Two questionnaires including Pargament’s questionnaire for evaluation of religious coping and the Beck depression inventory were used. Data analysis was performed using multiple regression and correlation. RESULTS: There was no significant difference between men and women in the mean score of avoidant relationship with God and alternate fearfulness and hopefulness (ambivalence coping style). But the mean score of relationship with God in women was higher than men. The rate of depression was higher among patients who had an avoidant strategy. The religious coping method of relationship with God was effective in reducing depression. The rate of depression was lower among patients whose families had a better attitude to religion. CONCLUSIONS: Psychotherapy, individual/familial counseling, and especially increasing of religious beliefs such as praying and trust in God, as well as increasing the knowledge of patient and his/her family cause better acceptance of the disease and better confrontation of psychological problems.