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Summary Background Oral leukoplakia is a precancerous disorder that is common among residents in Linxian. However, the associations between oral leukoplakia and upper gastrointestinal cancers have not been reported. We investigated the relationships between oral leukoplakia and upper gastrointestinal cancers in the Linxian General Population Trial cohort. Methods The Linxian General Population Trial cohort, with 29,584 healthy adults enrolled in 1985 and followed through the end of 2012. With collected baseline data, hazard ratios (HR) and 95% confidence intervals (95% CI) for developing upper gastrointestinal cancers were estimated using Cox proportional hazard models. Results During 28 years of follow-up, we confirmed a total of 2924 incident esophageal squamous cell carcinoma (ESCC) cases, 1644 gastric cardia cancers and 590 gastric non-cardia cancers. Overall, participants with oral leukoplakia had significantly higher risk of developing ESCC (HR = 1.18, 95% CI: 1.08, 1.29). Among individuals ⩽52 years old at baseline, oral leukoplakia was associated with elevated risk of ESCC (HR = 1.31, 95%CI: 1.15, 1.49). No significant associations were observed for gastric cardia or non-cardia cancers in either all subjects or subgroups. Conclusions Oral leukoplakia was associated with increased risk of ESCC, particularly in younger population. Future studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]