Purpose: The purpose of this study was to identify the factors influencing Symptoms of Stress in patients with chronic illness. Method: Data were collected by questionnaires from 1,748 patients with chronic disease in General Hospital in Seoul. Chronic diseases of were cardiac disease including hypertension, peptic ulcer, pulmonary disease included COPD and asthma, DM, and chronic kidney disease. The data were analyzed using descriptive statistics, pearson correlation coefficients, and stepwise multiple regression. Result: 1. The level of symptoms of stress was moderate(M=2.17). 2. The score of symptoms of stress showed significantly positive correlation with the score of mood state(r=.58, p=.00), perceived stress(r=.57, p=.00), and ways of coping(r=.33, p=.00). The symptoms of stress showed significantly negative correlation with the score of social support(r=-.37, p=.00) and self-esteem(r=-.19, p=.00). 3. The most powerful predictor of symptoms of stress was mood state and the variance explained was 34%. A combination of mood state, ways of coping, perceived stress, social support, and duration of illness account for 45% of the variance in symptoms of stress of the patients with chronic illness. Conclusion: This study suggest that mood state, ways of coping, perceived stress, and social support are significantly influencing factors on symptoms of stress of the patients with chronic illness.