This study is a single-blind randomized clinical trial that is done on 75 patients with multiple sclerosis referred to MS clinic of Ayatollah Kashani Hospital. After simple non-random sampling, participants were randomly assigned by minimization method to three groups: reflexology (25patients), relaxation (25 patients) and control (25 patients). In the experimental groups was performed foot reflexology and relaxation intervention (Jacobson and Benson) within 4 weeks, twice a week for 40 minutes and the control group were received only routine medical treatment as directed by a doctor. Data was collected via Demographic information questionnaire, fatigue severity scale (FSS), numerical pain scale (NRS) and questionnaire (DASS-21), before, immediately after and two months after interventions in all three groups.