BackgroundFew studies have examined the risk of gastrointestinal cancers in screen‐detected gallstone disease. This study aimed to investigate the association between screen‐detected gallstone disease and gastrointestinal cancers using the Kailuan cohort, a population‐based prospective cohort initiated in 2006.MethodsA total of 79 809 men who underwent gallbladder ultrasonography, were free of cancers in 2006 and did not have gastrointestinal cancers within one year were enrolled. A Cox proportional hazards model with age as the timescale was used to evaluate the association between screen‐detected gallstone disease and gastrointestinal cancers.ResultsWe identified 1264 cases with gastrointestinal cancers, including 303 cases with liver cancer and 94 cases with pancreatic cancer. Screen‐detected gallstone disease increased the risk of liver cancer, with an HR of 2.28 [95% confidence interval (CI): 1.20‐4.33, P = .012]. The association was modified by the hepatitis B surface antigen status. A non‐significant positive association was observed between pancreatic cancer and gallstone disease (HR 2.19, 95% CI: 0.95‐5.05, P = .065). However, the HR became significant after those individuals with diabetes were excluded (HR 2.60, 95% CI: 1.12‐6.01, P = .026).ConclusionScreen‐detected gallstone disease may predict the risk for liver and pancreatic cancer.