BACKGROUND Very few analytical studies are available on any association between stressful life events (SLE) and colorectal cancer (CRC), at least in Iran. The aim of this case control study was to determine the association between stressful life events (SLE) and colorectal cancer. MATERIALS AND METHODS This study was conducted in four hospital colonoscopy units in Tabriz city of Iran including 414 participants aged 40-75 years: 207 cases with CRC confirmed by pathology and colonoscopy findings and 207 controls free of neoplastic conditions were selected (from the same hospitals at the same period for the cases and after matching for age and sex). Stressful life events were assessed using a 43-item Holmes and Rahe Life Events Questionnaire. Multivariate logistic regression was used to estimate adjusted odds ratios for SLE and risk of CRC. RESULTS The stressful life event mean score in the case group was 141.3, in contrast to 63.8 in the control group (p<0.011). After adjusting for confounders, death of dear ones increased the risk of CRC (OR: 2.49; 95%CI: 1.41-5.13). Other types of stressful life events (family and husband disputes, serious occupational problems, unemployment of >6 months, and Serious financial problems) were also associated with CRC, but without statistical significance. CONCLUSIONS According to our findings, it seems that SLE may increase the risk of CRC.