Author summary Why was this study done? ➢ The burden of colorectal cancer (CRC) in China has been growing in recent years. ➢ More specific selection of individuals to undergo colonoscopy, based on both questionnaire-based risk assessment and fecal immunochemical test (FIT) results, could result in more efficiency allocation of colonoscopy resources. ➢ There is limited evidence on the colonoscopy screening yield when combining FITs and risk assessment through questionnaires. What did the researchers do and find? ➢ We calculated the baseline screening yield, participation, and cost per case detected in a national CRC screening program with a combined questionnaire-based risk assessment–FIT strategy. ➢ The baseline screening yield and participation rate were improved in the combined risk assessment–FIT group compared with risk factor assessment only group. ➢ The cost per CRC detected was $24,849 by the combined risk factor–FITs strategy, which was much lower than by the risk factor strategy ($55,846). What do these findings mean? ➢ A combined CRC screening strategy is feasible in China. ➢ The association between the combined RF-FIT strategy with CRC incidence and mortality reduction should be evaluated after long-term follow-up.