Background and Aims Long non-coding RNA nuclear-enriched transcript 1 (lncRNA NEAT1) is dysregulated in a variety of solid tumors and closely related to poor prognosis, but its relationship with the prognosis of patients with digestive system malignancies is still not clear. Therefore, this study was conducted to investigate the effect of lncRNA NEAT1 on the prognosis of patients with malignant tumors of the digestive system and its relationship with clinicopathologic features by systematic review and Meta-analysis.Methods The published cohort studies on the relationship between lncRNA NEAT1 expression and the prognosis or clinicopathologic characteristics of patients with digestive system malignancies were collected by searching the PubMed, Web of Science, Cochrane Library, China Knowledge Infrastructure and Wanfang databases. The search period was from the inception of the databases to 18th October 2021. Literature screening was performed by two investigators according to the inclusion and exclusion criteria, and the relevant data were extracted. Stata 12.0 software was used for statistical analysis.Results A total of 20 studies involving 2 031 patients with malignant tumors of the digestive system were finally included. The NOS scores of the included studies ranged from 6 to 9, of which 16 studies reported overall survival (OS), 5 studies reported disease-free survival (DFS), and 19 studies reported clinicopathologic features. Meta-analysis revealed that the OS (HR=1.66, 95% CI=1.41-1.97, P<0.001) and DFS (HR=2.0, 95% CI=1.51-2.65, P<0.001) of patients with digestive system malignancies and with higher NEAT1 expression were lower than those of patients with lower or no NEAT1 expression. The results of subgroup analysis according to survival analysis methods, NEAT1 expression cut-off values, number of samples, and follow-up time showed that the OS of patients with high NEAT1 expression were all significantly decreased (all P<0.05). In addition, the results of clinicopathologic characteristics analysis revealed that patients with higher levels of NEAT1 had a high risk of large tumor diameter (OR=2.20, 95% CI=1.73-2.79, P<0.001), advanced clinical stage (OR=3.10, 95% CI=1.95-4.92, P<0.001), lymph node metastasis (OR=1.94, 95% CI=1.30-2.90, P=0.001) and distant metastasis (OR=2.58, 95% CI=1.88-3.54, P<0.001), but it was irrelevant to the age, sex, tumor differentiation and vascular invasion of patients (all P>0.05).Conclusion The high expression of lncRNA RNA NEAT1 is an adverse prognostic factor for malignant tumors of the digestive system, and is also closely associated with unfavorable clinicopathologic features, which may be used as an important reference index for monitoring the condition and prognosis of malignant tumors of the digestive system.