Identifying individual and social factors affecting MS patients’ quality of life can play a significant role in planning, treatment process and modifying their lifestyle. Thus, this study proposed a structural model explaining MS patients’ quality of life based on health-promoting lifestyle with the mediating role of psychological capital. The study had a correlational design.  The population of the study was comprised of all MS patients who were members of Mazandaran Province MS Associations (including Sari, Amol, Nowshahr & Chalus, Tonekabon, and Ramsar) from among whom 305 patients were selected and studied via purposeful sampling. The instruments included the Multiple Sclerosis Impact Scale (MSIS-29) (Hobart et al., 2001), the Health-Promoting Lifestyle Profile (Walker et al., 1987), and Psychological Capital Questionnaire (Luthans, 2007). The data were analyzed using structural equation modeling and via AMOS26 software. The results indicated that the direct path quotients between health-promoting lifestyle and quality of life (P=0.001, β=-0.809), also, between psychological capital and quality of life (P=0.001, β=-0.839) were negative and significant at 0.01 level of significance. Furthermore, the indirect quotient between promoting lifestyle and quality of life was negative and significant at 0.01 level of significance (P=0.001, β=-0.498). In conclusion, a healthy lifestyle interacting with positive psychological resources such as hopefulness, optimism, self-efficacy, and resilience can cause adaptability of the patients to the disease during hard times of their lives and improve their quality of life.