Introduction: The goal of this research was to compare Alexithymia and psychological defense mechanisms in cancer patients with normal group. Also, investigation of the predictive role of three defense mechanisms in Alexithymia was considered. Materials and Methods: From chemotherapy ward of Shahid Beheshti hospital of Qom city, 45 cancer patients were selected by convenient sampling method. Also, 45 employees of this hospital were included as the normal group. Defense Mechanisms Questionnaire and Toronto Alexithymia Scale-20 were used. Data was analyzed with Independent Sample T-test, Pearson Correlation and Multivariate Regression. Results: Compared with normal people, cancerous patients had higher scores in alexithymia (p=0.01), difficulty in emotions recognition subscale (p=0.03) and non-developed defense mechanisms (p=0.007). Non-developed defense mechanisms had significant relationships with alexithymia and difficulty in emotion’s recognition and description subscales (p>0.01), also non-developed defense mechanisms could predict alexithymia in cancerous patients (p>0.005). Conclusions: Findings indicates that cancer is a stressful event that can cause non-developed defense mechanisms start to emerge as dominant psychological defense mechanisms in the majority of patients. Alexithymia which has a relation with defense mechanisms is also a dynamic reaction for coping with unpleasant emotions driven by the illness.