Background Multiple Sclerosis (MS) is associated with poor quality of life (QOL). Individuals suffering from MS must make multiple adjustments as their condition changes. To date, little is known about the role of psychosocial adjustment in improving QOL of patients with MS. Purpose The purpose of this study is to identify the relationship between psychosocial adjustment and HRQOL controlling for demographic variables among patients with MS. Methods This study used a descriptive-correlational design. A sample of 160 patients from two hospitals participated in the study. Self-reported data were collected using the demographic survey, Multiple Sclerosis Quality of Life (MSQoL-54) tool and Psychosocial Adjustment to Illness Scale–Self Report (PAIS-SR). Results Participants reported poor QOL and difficulty with psychosocial adjustment. The QOL and psychosocial adjustment were correlated with various demographic variables. After controlling for demographic variables, psychosocial adjust