BACKGROUND: To fully realize efficacy in cancer screening, timely and appropriate treatment for participants with malignant lesions is critical. However, the health-seeking behavior of patients with upper gastrointestinal (G.I.) cancer identified in population-level screening programs in China is unknown. METHODS: A community-based real-world investigation was conducted with 136 upper G.I. cancer patients detected in a large screening cohort in an area of high-risk for upper G.I. cancer in China. Using local medical claims data and semi-structured face-to-face interview, we collected information regarding the clinical treatment regimen and factors which result in the lack of timely and appropriate treatment. FINDINGS: The treatment records for 133 upper G.I. cancer patients were acquired. Among these, 48 (36•09%) patients did not receive treatment within three months of initial diagnosis, and treatment of early-stage cancer was more likely to be delayed. Sixteen patients did not seek further diagnostic testing due to their low health-awareness and socio-economic status. Another 20 participants proactively sought further diagnostic evaluation in health care facilities but were prevented from receiving further treatment due to low sensitivity of given diagnostic test(s), failure to recognize the significance of screening results, and/or lack of basic knowledge of diagnosis and treatment for early cancer on the part of clinicians. The treatment regimen offered to patients depended largely on the level of health care facilities they visited, and non-medical factors were the main reasons for choice of health care facilities. INTERPRETATION: A coordinated, system-based management strategy is urgently needed to support the design of upper G.I. cancer screening programs in rural populations in China. FUNDING: The Charity Project of the National Ministry of Health (201202014), the National Key R & D Program of China (2016YFC0901404), the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), and the National Natural Science Foundation of China (82073626).