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Background: Patients with multiple sclerosis (MS) suffer from a wide range of psychological problems. Application of a valid and reliable tool for psychosocial assessment is required for Iranian patients. The aim of this study is to determine the psychometric properties of the Persian version of the PARADISE-24 questionnaire in Iranian patients with multiple sclerosis. Methods: One hundred and thirteen multiple sclerosis cases were enrolled in this study. Participants were asked to answer the valid and reliable Persian version of the fatigue severity scale, social support scale, Pittsburg sleep quality index, and hospital anxiety and depression scale and translated version of the PARADISE-24 questionnaire. Twenty cases filed the questionnaire 2 weeks later to assess reliability. The intraclass correlation coefficient, Cronbach's alpha, correlation coefficients, and multiple regression analysis were used. Results: Mean age and mean duration of the disease were 35.8 ± 9.9 and 8.7 ± 5.6 years, respectively. The intraclass correlation coefficients ranged from 0.8 to 0.94 and Cronbach's alpha values (Cronbach's alpha was calculated as 0.91 for the whole questionnaire) were also significant. There were significant correlations between PARADISE-24 score and expanded disability status scale (r = 0.42, P < 0.001), fatigue severity scale (r = 0.62, P < 0.001), anxiety (r = 0.43, P < 0.001) and Pittsburg sleep quality index scores (r = 0.46, P < 0.001). Regression analysis by considering PARADISE-24 as dependent and other variables as independent showed that expanded disability status scale, fatigue severity scale, anxiety score, and Pittsburg sleep quality index were positive predictors of PARADISE-24 score. Conclusions: Persian version of PARADISE-24 questionnaire is a valid and reliable instrument for evaluating psychosocial aspects in patients with multiple sclerosis.