BACKGROUND: Colorectal cancer (CRC) is the third most common cancer globally, with rising incidence in developing countries due to lifestyle and dietary shifts. CRC often presents with late-stage symptoms, leading to higher mortality. Early detection through screening can significantly improve survival rates. In Syria, CRC is the second most common cancer, but screening rates remain low, especially following the decade-long war. This study aims to assess the knowledge of CRC and evaluate the awareness of CRC screening among Syrians to guide prevention and detection strategies. METHODS: A cross-sectional online survey was conducted from September 27 to October 21, 2023, across six governorates: Damascus, Homs, Aleppo, Latakia, Hama, and Tartus, using a self-administered questionnaire distributed via social media. Statistical analysis was performed using SPSS v28.0, with a Chi-square test to explore differences in knowledge based on socio-demographical factors. Multicollinearity was assessed using the Variance Inflation Factor (VIF), and multinomial regression was performed to confirm relationships established by the Chi-square analysis. RESULTS: The study included 772 participants, 42.6% of whom were aged 30-35 years. The majority were female (64.4%) and married (56.3%). Only 27.8% considered themselves informed about CRC. While 54.8% had heard of colonoscopy, only 15.4% had undergone the procedure. Significant knowledge gaps were identified, particularly regarding the link between adenocarcinoma polyps and CRC (29.9%), the role of diet (33.2%), and the protective effect of aspirin (17.7%). Individuals aged 50 and above demonstrated higher awareness levels, particularly in recognizing CRC's hereditary nature (p-value = 0.033) and the potential for cure (p-value = 0.012). Education and economic status were also strongly associated with better CRC knowledge, and males generally exhibited higher awareness than females. CONCLUSION: This study highlights significant gaps in CRC knowledge and screening awareness among Syrians, emphasizing the need to integrate education and complimentary screening into national health policies. Targeted campaigns, nonprofit collaboration, and media engagement are essential to bridge these gaps. Future research should address limitations like sampling bias and the cross-sectional design through longitudinal and comparative studies to guide tailored interventions.