Background: Colorectal cancer is a common type of cancer in Saudi Arabia and globally. Timely screening is needed to improved treatment outcomes. The success of colorectal cancer (CRC) depends on the compliance by the targeted population. The aim of this study is to determine how patients’ knowledge, beliefs, behavior, self-efficacy, and barriers affect CRC screening. Materials and Methods: A cross-sectional study design was used. A total of 925 patients were recruited as participants from 38 hospitals in Riyadh, Jeddah, Makkah, Dammam, Al Ahsa, and Albaha. Data was collected using questionnaire delivered to the participants. Results: Most of the participants (over 95%) were aware of CRC. More than half knew about CRC screening. However, response to screening programs was low due to the lack of knowledge, fear, and insufficient patient awareness programs. Conclusion: Majority of the patients are willing to get regular CRC screening. However, there are low rates of actual screening due to fear and embarrassment, lack of knowledge, and other barriers. Healthcare workers need to intervene by creating enough public awareness.