Gastrointestinal cancers are the most common type of cancer affecting humans. High expression of HOTAIR, a lncRNA, in various types of different tumors may be associated with poor prognosis. In this study, we performed a meta-analysis of the relationship between HOTAIR expression and gastrointestinal cancers. Five databases were comprehensively searched for all literature until January 2023. Moreover, the target genes of HOTAIR were predicted by co-expression analysis based on the TCGA gene expression matrix for six gastrointestinal cancer types. Finally, the mechanism through which HOTAIR affects tumors of the digestive system was systematically reviewed. Our results showed that the high HOTAIR expression group had worse outcomes with a pooled hazard ratio (HR) of 1.56 (95% CI = 1.38–1.75, P < 0.001). Furthermore, HOTAIR was identified as an unfavorable prognostic factor for overall survival in the esophageal carcinoma (ESCA) and gastric cancer (GC), as the HR were 1.94 and 1.58, respectively. The high correlation between the expression of HOXC family genes and HOTAIR, with correlation coefficients of 0.863 (HOXC11), 0.664 (HOXC10), 0.645 (HOXC8), and 0.581 (HOXC12). The ‘cell cycle’ pathway and pathways relating to infections, namely ‘herpes simplex virus 1 infection’ and ‘complement and coagulation cascades’ were significantly enriched in KEGG analysis. Also, we perform a systematic review to summarize the related oncogenic mechanism of HOTAIR. In conclusion, the HOTAIR has been identified as a potential prognostic factor in patients with gastrointestinal cancers.