The association between Parkinson's disease (PD) and gastrointestinal (GI) cancers remains unknown. This study aims to assess the causal effect of PD on colon cancer (CC), gastric cancer (GC), esophageal cancer (EC), and rectal cancer (RC) using the two-sample Mendelian randomization (MR) method.Five pairs of summary datasets of genome-wide association studies (GWAS) from publicly available studies [Integrative Epidemiology Unit (IEU) OpenGWAS project, FinnGen, and GWAS Catalog database] were enrolled. The inverse variance weighted (IVW) method was used as the primary outcome for MR analysis. Cochran Q-derived, MR-Egger intercept test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods, and leave-one-out analysis were used to test heterogeneity and directional pleiotropy.For the European population, no significant causal effect of PD on the risk of CC was found [odds ratio (OR) =0.9; 95%, confidence interval (CI): 1.00-1.11; P=0.42]. The same applied to the East Asian population (OR =1.05; 95% CI: 0.66-1.66; P=0.63). As for GC, no causal effect was found (OR =0.94, 95% CI: 0.89-0.99; P=0.22). Moreover, the genetic liability for PD was not associated with EC (OR =1.00; 95% CI: 0.99-1.00; P=0.32). Finally, no evidence was found for any causal effect of genetic liability for PD on an increased risk of RC (OR =1.00; 95% CI: 0.99-1.00; P=0.71).There is no causal effect of genetic liability for PD on an increased risk of GI cancer.2024 Journal of Gastrointestinal Oncology. All rights reserved.