Background: The special AT-rich sequence-binding proteins 1 (SATB1) is a major regulator involved in cell differentiation. It has been shown that SATB1 acts as an oncogenic regulator. The clinical and prognostic significance of SATB1 in gastrointestinal cancer remains controversial. The purpose of this study is to conduct a systematic review and meta-analysis to elucidate the impact of SATB1 in gastrointestinal cancer. Results: A total of 3174 gastrointestinal cancer patients from 15 studies were included. The correlation between SATB1 expression and OS or RFS was investigated in 12 and 5 studies respectively. The results of meta-analysis showed that SATB1 overexpression is inversely correlated with OS (combined HR: 1.79, p = 0.0003) and RFS (combined HR: 2.46, p < 0.0001). In subgroup analysis, SATB1 expression is significantly correlated with poor prognosis in gastrointestinal cancer in Asian population. SATB1 expression is associated with stage, invasion depth, lymph node metastasis and distant metastasis. Methodology: Published studies with data on overall survival (OS) and/or relapse free survival (RFS) and SATB1 expression were searched from Cochrane Library, PubMed and Embase (up to Dec 30, 2016). The outcome measurement is hazard ratio (HR) for OS or RFS related with SATB1 expression. Two reviewers independently screened the literatures, extracted the data and performed meta-analysis using RevMan 5.3.0 software. The combined HRs were calculated by fixed-or random-effect models. Conclusions: The results of this meta-analysis suggest that SATB1 overexpression is related to advanced stage, lymph node metastasis and distant metastasis. SATB1 overexpression is a marker indicating poor prognosis in gastrointestinal cancer.