Background: Colon cancer screening (CRCS) uptake is markedly affected by public awareness of the disease. This study was conducted to assess levels of knowledge of CRC, to explore the pattern of CRCS uptake and identify possible barriers to screening among Saudis older than 50 years of age and primary care providers (PCPs) in Al Hassa region, Saudi Arabia. Materials and Methods: This cross-sectional study was conducted in randomly selected primary health care (PHC) centers, 884 Saudis and 39 PCPs being enrolled for data collection. Structured interviews were conducted to obtain information regarding socio-demographic characteristics, personal information relevant to CRC, awareness about early signs/symptoms and risk factors, and barriers to CRCS. Also, a self-administered data collection form was used to assess barriers to CRCS from the physicians' perspectives. Results: More than 66% of participants were lacking knowledge about CRC. Participants with higher educational levels, having ever heard about CRC, and having relatives with CRC had a significantly higher awareness of the disease. The rate of reported CRCS was low (8.6%). After conducting a logistic regression analysis, it was observed that female gender (OR=0.28; 95% CI=0.14-0.57; P=0.001), being unmarried (OR=0.11; 95% CI=0.10-0.23; P=0.001), lower levels of education (OR=0.36; 95% CI=0.16-0.82; P=0.015), and having no relatives with CRC (OR=0.30; 95% CI=0.17-0.56; P=0.001) were significantly associated with a lower CRCS uptake. There was a significant difference between most of the perceived barriers to CRCS and gender. Exploratory factor analysis showed that personal fear (especially fear of the screening results and shyness) was the major factor that hindered CRCS with high loading Eigen value of 2.951, explaining 34.8% of the barriers of the included sample toward utilization of CRCS, followed by lack of awareness of both person and providers (high Eigen value of 2.132, and explaining 23.7% of the barriers). The most frequently cited barriers to CRCS from the physicians' perspectives were lack of public awareness, lack of symptoms and signs, and fear of painful procedures. Conclusions: Poor levels of knowledge about CRC were found among older Saudis attending PHC centers in Al Hassa, Saudi Arabia. It is crucial to implement an organized national screening program in Saudi Arabia to increase public awareness.