Background: Colorectal cancer (CRC) is the most common cancer diagnosed worldwide. CRC can be effectively prevented or treated if detected early, through screening. Purpose: This study aimed to determine the influencing factors of CRC screening participation in 50-70-year adults in Iran. Method: A total of 354 adults who never participated in the CRC screening from two health centers in Isfahan in September 2022 were selected randomly. A group of 329 sex and age-matched adults with a history of CRC screening was selected as a control group. Logistic regression analyses were applied to assess the cognitive differences between the two groups. Results: According to the results, Knowledge (OR = 1.61, 95% CI:1.36-1.9), perceived susceptibility (OR = 1.17, 95% CI:1.04-1.3), response efficacy (OR = 1.24, 95% CI:1.09-1.41), and self-efficacy (OR = 1.13, 95% CI:1.06-1.2) among the control group and perceived barriers (OR = 0.88, 95% CI:0.85-0.92) in the case group, were significant factors influencing participation in the CRC screening. Discussion Results of this study suggest that an HBM education model is an advantageous approach to increase CRC screening participation in adults. Translation to Health Education Practice: Certified Health Education Specialists are key personnel in using the HBM model of care and facilitators of behavioral change that will be resulted in improved participation in CRC screening.