Lysosomal associated membrane protein 3 (LAMP3) is a newly identified tumor-specific protein. It is a downstream target gene of tumor suppressor TP53 and its expression has been associated with hypoxia-induced metastasis and poor overall survival in cervical and breast cancers. However, little is known of LAMP3 protein expression in gastrointestinal cancer and its prognostic value. We determined protein expression of LAMP3 and TP53 in both gastric (n=750) and colorectal (n=479) tissues by immunohistochemistry analysis on tissue microarray (TMA), their expression was correlated with patients' clinical parameters. LAMP3 and TP53 protein expression was significantly higher in cancerous tissues compared to normal and benign tissues. In both gastric and colorectal cancers, high LAMP3 protein expression (LAMP3+) was significantly associated with tumor stage (P=0.014 and P<0.001). No correlation between LAMP3 and TP53 expression was observed. Patients with high LAMP3 expression but not high TP53 expression had a poor overall survival (for gastric cancer P<0.001, CI: 1.762-4.567; for colorectal cancer P=0.036, CI: 1.062-5.980). Our data suggest that epithelial LAMP3 expression is an independent prognostic marker for gastrointestinal cancer.