This study was conducted to investigate the relationship between lifestyle factors and colorectal cancer in the men and women with colorectal cancer in the city of Yazd. Results of univariate analysis showed a significant association between the family history of colorectal cancer in the first-degree relatives and second-degree relatives with colorectal cancer. The Family history of colorectal cancer did not remain in the logistic regression model with the presence of other variables. Dehganzadeh et al. [
4] and Safaei et al. [
3] did the research and the results showed that the family history of colorectal cancer in first-degree relatives increased the risk of colorectal cancer 35.4 and 2 times, respectively. Our study showed a significant association between smoking and colorectal cancer and the results of the regression model showed that smoking increases the risk of developing colorectal cancer by 7.79 times. He et al. showed in their study the odd ratio of effecting with colorectal cancer is 1.32 in smokers [
8]. The results of our study showed that there was not any significant association between the consumption of hookah and opium with colorectal cancer and this is constant with the results of Moshfeghi et al. [
9] and Kim et al. studies [
10]. Many individuals with addictive behavior don’t report taking drugs and hide it therefore, it is estimated that the consumption of opium is more than it is reported. It was believed that physical activity reduces the risk of colorectal cancer by increasing bowel peristalsis that reduces the duration of the exposure of food pathogens to the intestinal wall [
11]. Results of univariate analysis showed a significant protective association between physical activity and colorectal cancer that is consistent with Lee et al. [
12] and Dehganzadeh et al.’s study [
4]. Most of the time in women, colorectal cancer occurs along with ovarian and endometrial cancers. The findings of Park’s study showed that in patients with colon cancer, the risk of uterine cancer and ovarian cancer, increases by 43% and 9 - 19% increase, respectively [
13]. Our result showed a significant relationship between a history of uterine cancer and gastric cancer among subjects in the case and control groups therefore, the history of uterine and gastric cancer was significantly higher in the people of the case group than the control group. However, in none of the subjects history of ovarian cancer was observed. It was confirmed that Crohn’s disease and ulcerative colitis are inflammatory bowel diseases which are effective in the cause of colorectal cancer. Results of univariate analysis showed that inflammatory bowel disease increased the risk of colorectal cancer that is consistent with the previous studies [
4,
14]. Our study showed a significant association between diabetes and colorectal cancer and the results of the regression model showed that diabetes increases the risk of colorectal cancer up to 7.31. The results of the meta-analysis study conducted by Larsson et al. showed that diabetic patients have a 30% increased risk of developing colon cancer compared to non-diabetic patients that is consistent with our findings in this study [
15]. In this study, samples were taken from alive people and those who were accessible. The ones who demised and migrated were excluded from the study .Also, due to the ethical issues and the high cost of diagnosing of colorectal cancer, the absence of colorectal cancer in the control group, was based on the self-report of individuals. Therefore there might have been an error in this study. The results of our study showed that smoking and diabetes can significantly increase the risk of colorectal cancer. With the changes in behavioral habits, such as giving up smoking and prevention or treatment of diabetes, the rate of occurrence of colorectal cancer will reduce. In general, it is suggested to reach more accurate results, performed studies with a prospective design and larger sample size.