Aims Menopause is one of the most critical periods in women’ s lives that although it is a physiological event, but it is accompanied by complications that affect women’ s quality of life. The aim of this study was to determine the prediction of the quality of life of menopausal women based on health literacy and self-efficacy. Instrument & Methods This cross-sectional descriptive-analytical study was conducted on 400 postmenopausal women referred to comprehensive health centers in Mashhad in 2018 who were selected by random cluster sampling method. The research tool was a 4-part questionnaire including demographic characteristics, test of functional health literacy in adults (TOFLA), Sherer general self-efficacy and quality of life in menopause. Data were analyzed by SPSS 22 software using Kruskal-Wallis, Mann-Whitney, Spearman’ s correlation, and linear regression model. Findings There was a significant correlation between health literacy (r=-0. 352) and selfefficacy (r=-0. 338) with quality of life (p<0. 001). Self-efficacy, health literacy, marriage age, type of delivery, vitamin D consumption, dairy consumption, and fruit were predictors of quality of life in menopausal women (p<0. 05). Self-efficacy and health literacy predicted 18% and the other variables predicted 31% of variance in quality of life. Conclusion Health literacy and self-efficacy are two factors affecting the quality of life of postmenopausal women.