Objective: According to the Common-Sense Model of Self-Regulation, when faced with a health threat, we make cognitive and emotional assumptions about the illness. The aims of this study were to (a) examine the role of sociodemographic and disease-specific factors on illness perception and perceived stress and (b) test the association between perceived stress and illness perception in participants diagnosed with gastrointestinal cancer. Methods: Participants completed a battery of questionnaires including a Sociodemographic and Disease-Specific Questionnaire, the Illness Perception Questionnaire, Brief Version (Brief-IPQ), and the Perceived Stress Scale (PSS-14). Descriptive statistics, Pearson correlations, analysis of variance (ANOVA), and linear regression were performed to test the hypotheses. Results: Of the 627 participants, the mean age was 62 years (SD = 11); the majority were male (63.3%) and Caucasian (90.9%). Younger (F3,625 = 5.80, P <.01) and divorced or never married participants reported higher levels of perceived stress when compared with older and married participants (F4,618 = 3.52, P <.01). Younger participants (18-74 years old) reported more negative illness perceptions than older participants (75 years and older) (F3,511 = 4.08, P <.01). A weak, positive relationship between perceived stress and illness perceptions was observed (r = 0.22, P <.01), and illness perceptions predicted 36.1% of the variance of perceived stress. Conclusions: Our findings suggest that participants who negatively perceived their illness experienced greater levels of perceived stress. Interventions that aim to adjust patients' illness perceptions in order to facilitate a reduction of stress and improvement in quality of life are needed.