Introduction: the role of cognitive, metacognitive and metaemotional factors in psychological distress has been clearly confirmed. The current research study aims to examine a psychological distress model based on intolerance of uncertainty and emotional schemas of cancer patients with the mediating role of metacognitive beliefs and cognitive avoidance. Method: regarding the methodology, the present study relies on correlation and structural equation modeling. The study sample included 300 cancer patients who visited various hospitals in Tehran and completed the questionnaires of uncertainty intolerance, stress, depression and anxiety, emotional schemas, metacognitive beliefs, and cognitive avoidance. Results: findings demonstrated that the proposed model has appropriate fitness among cancer patients. Also, the relationship between mediating variables and endogenous and exogenous variables is significant. The variables under investigation explained 46 percent of psychological distress variance in the patients. Conclusion: Psychological distress in cancer patients is affected by interaction of excessive emotional states, intolerance of uncertainty, such as metacognitive beliefs and emotional schemas.