The aim of this work is to investigate and analyze the main factors that influence the quality of life (QOL) of multiple sclerosis (MS) patients. The QOL (Multiple Sclerosis Impact Scale), disability (Expanded Disability Status Scale), fatigue (Modified Fatigue Impact Scale) and depression (Beck Depression Inventory) were assessed in 100 MS patients. Correlation analysis shows that QOL is positively correlated with disability status, fatigue and depression, i.e. the more severe the disability, fatigue and depression, the worse the QOL. Multiple linear regression analysis indicated that Expanded Disability Status Scale grade and fatigue have important predictive value on the somatic QOL of MS patients. On the other hand, depression and fatigue have important predictive value on the mental QOL of MS patients. The QOL of MS patients is influenced by various factors, nursing care that focuses on patient disability, fatigue and depression should be strengthened. Copyright © 2012 John Wiley & Sons, Ltd.