Screening is an effective measure to prevent and control colorectal cancer (CRC). A mass CRC screening programme was conducted in Guangzhou from 2015 to 2017. Public media and reminders from a mobile short message service were used to invite residents aged between 50 and 74 years. A high-risk factor questionnaire (HRFQ) and biennial faecal immunochemical testing (FIT) were chosen as the primary screening methods, and individuals with a positive test result were referred to a defined hospital for an assessment colonoscopy. During the 3 years, 350,581 residents of the total eligible population of 2,283,214 attended the free first stage of screening. In all, 91.0% of the participants finished the HRFQs and FITs. The total uptake rate was 15.4%, which increased with age, female sex, and rural location. There was 15.9% positivity in the first stage of screening, including 8.5% positive HRFQs, 6.2% positive FITs and 1.2% positive HRFQs and FITs. In total, 10,600 individuals with positive HRFQs/FITs completed an assessment colonoscopy. The total uptake rate of colonoscopies was 18.9%, which decreased with age and female sex. Three hundred fifty-one CRCs and 980 advanced adenomas (AAs) were diagnosed with positive predictive values (PPV) of 3.3% and 9.2%, respectively. The PPVs of CRCs in the exclusively FIT-positive population were 4.9%, which was 10 times greater than in the exclusively HRFQ-positive population (0.5%). The PPVs of CRCs and AAs increased with age and male sex. The detection ratio of localized CRCs (including stage I and stage II) increased 68.1% due to screening. Although the compliance rate was low, the PPVs for CRCs and AAs were high. More effective mobilization of the programme's needs and subsidies for colonoscopies should be taken into account to increase compliance.