Introduction: Multiple sclerosis is a progressive neurological disease is most common in young adults. This disease has created many problems for patients and it leads to disability and dependence in life. Clinical findings indicate that mental stress of everyday life events gradually work different body systems including the immune system is affected and can weaken it. Various factors can modulate or enhance the effect. This study aimed to investigate the relationship between cortisol levels and components of TGF-B with five personality factors have been conducted in patients with multiple sclerosis. Materials and Methods: This study is a comparative study included 100 patients (27 men and 73 women) of patients with multiple sclerosis referred to the support forum of MS patients in Mashhad city that were selected available sampling. The research tools include NEO Personality Inventory short form and blood sampling to determine the levels of cortisol and TGF-B was carried out on patients. The data was used for the analysis of indicators and statistical methods including mean, standard deviation and test T. Results: In the five-factor personality dimension neuroticism only significant difference between male and female patients. The results also showed a significant difference between personality factors and levels of cortisol (p=0/001). There was also a significant relationship between personality factors and TGF-B (p=0/09). Conclusion: Psychotherapy with consideration of the traumatic personality traits can be effective in the treatment of physical symptoms in patients with multiple sclerosis.