Colorectal cancer is preventable and treatable by screening and early detection. Fecal immunochemical tests (FIT) for average risk individuals is an effective strategy for screening. Incidence and mortality in Mexico is increasing and large-scale screening programs do not yet exist. The aim of this study was to evaluate the feasibility of FIT-based colorectal cancer screening program in Mexico City. For more than 15 months, average risk individuals in Mexico City were invited to participate at Mexico's Instituto Nacional de Cancerologia (INCan, Mexico City, Mexico). Participants received an FIT kit for stool collection, results ≥20 ng/mL were referred for high quality colonoscopy. Participants' results were classified according to the most advanced clinical finding as: adenocarcinoma, high-risk adenomas, low-risk adenomas, serrated lesions, hyperplastic polyps, and no polyps. Sequential analyses were performed to assess the positive predictive value (PPV) of FIT. A total of 810 participants were eligible, 737 (91.0%) returned the FIT and 112 (15.2%) had an abnormal result. Of these participants, 87 (77.7%) completed colonoscopy. Clinical findings of participants included: seven (8.1%) adenocarcinomas, 18 (20.7%) high-risk adenomas, 23 (26.4%) low-risk adenomas, one (1.2%) serrated lesions, 14 (16.1%) hyperplasic polyps, and 24 (27.6%) no polyps. The PPV of FIT using the ≥20 ng/mL was 8.1% for cancer and 20.7% for high-risk adenomas. In conclusion, colorectal cancer screening with FIT is feasible at INCan in Mexico City, where resources are available. Further studies are needed to determine feasibility of colorectal cancer screening in other settings, as well as optimal hemoglobin detection cut-off points to maximize the population benefits of colorectal cancer screening with FIT in Mexico.