The human mental organization has a behavioral regulative principle that operates based on certain conscious and unconscious needs. Experience of stress disrupts human mental structure and results in symptoms of psychological and physical disorders. One source of stress is having ailing children. Accordingly, this study investigates self-regulation mediational processes in the context of perceived stress in mothers of children diagnosed with cancer. The convenience sample of this study consisted of 245 mothers, who volunteered to participate and were administered the following questionnaires: Integrative self-knowledge; Self-control Scale; Self-compassion Scale; perceived stress and Chronic Self-destructiveness Scale, body-symptoms checklist. Analysis of the survey data was carried out using structural equation modeling (SEM). The analysis suggests that perceived stress is mediated through self-regulation for self-destructiveness, physical symptoms, and unpleasant self-relevant through. Therefore, exposure to stress has destructive effects both in terms of physical symptoms and on an emotional and behavioral level. The authors concluded that self-regulation was a supportive variable, helping individuals cope better with unpleasant events, retrieve their ideal mental balance and maintain their mental organization. It is implied that based on a self-regulation model, effective management of one’s mental organization can improve an individual’s capacity to effectively cope with inevitable sources of stress.