Background: Multiple sclerosis (MS) is a disabling and chronic disease of the brain and spinal cord, causing a wide range of symptoms incuding muscle movement, balance and vision and leading to psychlogical disorders such as anxiety, depression and stress which have important consequences on lives of patints. But whether cognitive hypnotherapycould reduce the perceived stress and improve life quality of these patients? Aims: The purpose of this study was to investigate the effectiveness of cognitive hypnotherapy on reduction of perceived stress of patients with MS. Method: This research was a quasi-experimental study with pre, post and 2 months follow up test design with control group. The statistical population included 236 patients with replacing-remitting MS referred to a neurologist private clinic within period of January to June in the city of Tehran in 2018. Hence 30 patients among the statistical population were selected through convenience sampling based on inclusion and exclusion criteria, then placed randomly into two equal experimental and control groups. Perceived stress of participants of both groups was measured by Cohen perceived stress scale (Cohen & et. al, 1983) in 3 stages of pre, post and follow up tests. Individualized treatment based on protocol of effectiveness of cognitive hypnotherapy on reduction of perceived stress of patients with MS (established by reearcher, 2018) was done for experimental group in eight weekly 1 hour sessions. Data were analyzed at two levels of descriptive and inferential. Results:The results showed that cognitive hypnotherapy significantly reduced the mean scores of positive, negative and total perceived stresses of experimental group(P<0/01). Conclusions: Based on the results, cognitive hypnotherapy intervention is an effective method for stable reduction of the perceived stress in patients with multiple sclerosis.