Background: Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent. Methods: We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random-effects models. Results: Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case-control, and 3 case-cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone-binding globulin (SHBG) were associated with increased risk of gastric cancer (OR=1.35; 95%CI, 1.06-1.72), but such associations were restricted in men only (OR=1.43; 95%CI, 1.10-1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR=2.07; 95%CI, 1.40-3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR=2.10; 95%CI, 1.48-2.96), particularly in men (OR=2.63; 95%CI, 1.65-4.18), Asian populations (OR=3.27; 95%CI, 1.57-6.83) and in hepatitis B surface antigen-positive individuals (OR=3.90; 95%CI, 1.43-10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR=0.89; 95%CI, 0.80-0.98 and OR=0.88; 95%CI, 0.80-0.97, respectively) but not in women. Conclusions: Circulating levels of sex hormone-binding globulin and testosterone may influence the risk of gastric, liver, and colorectal cancer. Impact: Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment.