Special AT-rich sequence binding protein 1 (SATB1), a new type of gene regulator, has been reported to express in various human cancers and may associate with the malignant potential. However, there are few data available on SATB1 expression and its relationship to tumor progression in gastric cancer. The current study was designed to examine the SATB1 expression in gastric cancer and to correlate it with clinical outcome. SATB1 expression was studied by qRT-PCR, western blotting and immunohistochemistry, respectively. The correlations between SATB1 expression and clinicopathological factors were statistically analyzed. SATB1 mRNA expression was significantly up-regulated in gastric cancer specimens as compared with that in normal tissues (P<0.001). Overexpression of SATB1 protein was observed in gastric cancer cell lines by western blotting. Fifty-three (44.9%) cases showed positive staining for the SATB1 proteins by immunohistochemistry. The expression of SATB1 mRNA agreed well with the western blotting and immunohistochemical findings (P<0.001). SATB1 expression was positively correlated with age, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Moreover, Kaplan-Meier analysis revealed that SATB1 overexpression was associated with a significantly worse survival (P<0.001). Further multivariable analysis indicated that SATB1 expression was an independent prognostic indicator for gastric cancer (P=0.023). In summary, overexpression of SATB1 correlated with metastatic potential of human gastric cancer and would be a novel independent prognostic marker for predicting the outcome of gastric cancer.