Objective: To explore the cost-effectiveness and cost-benefit of colorectal cancer (CRC) screening from the perspective of health economics，so as to provide scientific basis for decision-making by health administrative departments. Methods: A total of 975 hospital patients aged 40-75 years were randomly selected to evaluate the cost-effectiveness and cost-effectiveness of CRC risk assessment questionnaire followed by sequential fecal occult blood plus colonoscopy，colonoscopy and MT-sDNA combined detection. Results: The overall positive rate of multi-target DNA detection was 26.32 %，and the compliance rate of colonoscopy was 48.00 %. The overall positive rate of fecal occult blood test was 29.25 %，and the compliance rate of colonoscopy was 67.74 %. The positive rate of MT-sDNA in males was higher than that in females (P=0.017). The positive rate of DNA detection increased with age (P=0.004). The average cost per case of adenomatous lesions and colorectal cancer was 7482.27 yuan and 30652.18 yuan，respectively. The benefit-to-cost ratios of MT-sDNA，colonoscopy and fecal occult blood + colonoscopy were 9.20，9.62 and 9.61，respectively. Conclusion: The multi-target fecal DNA test could be used for opportunistic screening of people with high willingness to pay. Through the CRC risk assessment questionnaire screening，sequential fecal occult blood test screening method had higher cost-effectiveness.