Background: Colorectal cancer is one of the most common malignancies worldwide with more than one million new cases. According to the Ministry of Health and Medical Education of Iran, colorectal cancer is the third most common cancer in Iran. Many risk factors are known causes of this disease. However, the molecular mechanisms associated with colorectal cancer are still under investigation. Recent studies have shown that some viruses, particularly human papilloma virus, may be associated with the pathology of colorectal cancer.Methods: This case-control study examined 95 colorectal cancer and 95 normal colon tissue paraffin blocks (control) to identify the relationship between human papilloma virus and colorectal cancer by polymerase chain reaction.Results: Clinicopathological data that included sex, age, tumor grade, stage and location were recorded. All tumor and control groups (totally: 190 samples) were negative in terms of the human papilloma virus genome. No relationship between clinico- pathological data and human papilloma virus genome was identified.Conclusions: Regardless of other risk factors for colorectal cancer, a number of studies in different parts of the world have shown that human papilloma virus may be an important factor in the increasing incidence of colorectal cancer. However, we have found no association between human papilloma virus and colorectal cancer in this study.