Background: Substance use disorders (SUDs) have a major negative impact on family caregivers in many aspects causing various burdens in quality of life while self-efficacy allows family caregivers to evaluate capability to control and manage caregiving stress and burden. Aim: This study aimed to assess the relationship between burden and self-efficacy among family caregivers of patients with substance use disorders. Design: A descriptive relational study design was utilized in this study. Setting: This study was carried out in the addiction outpatient clinic in Abassia mental health hospital affiliated to General Secretariat of Mental Health and ministry of health. Subjects: A sample of 140 family caregivers of patients with SUDs who full field specific inclusion criteria. Data collection tool: Data was gathered1) Interviewing Questionnaire includes three parts: a) patient and family caregiver's demographic data, b) history of SUDs, c) Knowledge about SUDs; 2) Burden of family caregivers for patients with substance use disorders; and 3) self-Efficacy Scale. Results: date analysis show that more than two thirds of the studied caregivers had severe level of caregiving burden, and more than three quarters of them had low levels of self-efficacy, also three fifths of them had unsatisfactory knowledge about SUDs. There was a highly significant negative correlation between family caregivers' burden and their self-efficacy. There was a high negative correlation between family caregiver's knowledge and their caregiving burden; also there was a high positive correlation between family caregiver's knowledge and their self-efficacy. Conclusions: caregivers with low self-efficacy and unsatisfactory knowledge regarding SUDs experienced severe level of caregiving burden. Recommendations: Designing and implementation of Psycho-educational program for family caregivers of patients with substance use disorder to enhance their self-efficacy, coping abilities and quality of life and to overcome their burden of caregiving.