Abstract Background and aim: Gastrointestinal (GI) malignancies are a global public health issue and are associated with many risk factors including genetic and lifestyle factors. The current systematic review and meta-analysis was conducted on analytical observational studies (case-control and cohort studies) to assess the association between main GI cancers and opium use. Methods: Three databases (PubMed, Web of Science, and Scopus) and the Google Scholar search engine were searched using relevant keywords. The quality assessment of the included studies was conducted with the ROBINS-E assessment tool. The frequencies of fixed effect and random effects (RE), and also Bayesian meta-analysis were conducted to evaluate the relationship between GI cancers and opium use based on the adjusted odds ratio (OR) estimates and their standard errors (or confidence interval in their absence) using the R software. Results: Of the 570 studies that were found in the primary search, 13 papers met our inclusion criteria and were analyzed in the meta-analysis. The results of fixed effect (OR:1.90; 95%CI:1.68-2.10) and random effect (OR:2.31; 95%CI:1.77-3.0) models showed a significant association between all types of GI cancer and opium use. This association was also observed in subgroup analyses that were based on the GI cancer type and study design. Conclusion: Our meta-analysis showed that opium use can increase the risk of GI cancers. Keywords: Opium, Gastrointestinal, Esophagus, Gastric, Colon, Pancreatic, Cancer