Objective: Recent studies have shown that distal-less homeobox 6 antisense 1 (DLX6-AS1) is aberrantly expressed in various cancers and is associated with poor prognosis. This meta-analysis is designed to investigate the effects of DLX6-AS1 expression on clinicopathological features and survival outcomes. Methods: All eligible studies were searched from Pubmed, Web of Science, Embase, the Cochrane Library, and Wanfang database, up to August 2019. The literature was selected according to the inclusion and exclusion criteria listed in this work, and the quality of each eligible study was assessed. Each patient’s clinicopathological features and survival data were analyzed using Stata12.0 software. Begg’s test and sensitivity analysis were also conducted. Results: A total of 12 articles were included, covering 841 patients. Results showed that high expression of DLX6-AS1 was significantly closely associated with poor overall survival in tumor patients (HR = 2.30, 95% CI: 1.70–3.09, P < 0.01). This meta-analysis also showed that overexpression of DLX6-AS1 was significantly associated with tumor stage (P < 0.01), tumor size (P < 0.01), lymph node metastasis (P < 0.01), and distant metastasis (P < 0.01). Begg’s test suggested no publication bias. Conclusion: This meta-analysis revealed that high expression of DLX6-AS1 was related to the advanced clinicopathological characteristics of human digestive system cancers (gastric cancer, esophageal cancer, colon cancer, pancreatic cancer and hepatocellular carcinoma) and other cancers such as ovarian cancer, osteosarcoma and non-small cell lung cancer, and DLX6-AS1 has important predictive value for poor prognosis. However, more studies are needed to further corroborate these findings.