Programmed cell death 5 (PDCD5) is a novel apoptosis-related gene with potent antitumor effects which can interact with the histone acetyltransferase Tip60 and induce DNA damage-induced apoptosis. Reduced PDCD5 expression has been found in a few types of human tumors and is also associated with the progression and prognosis of the tumors. However, the expression status and clinical significance of PDCD5 in gastrointestinal stromal tumors has not yet been analyzed. In our study, we examined PDCD5 expression in 63 tumor samples of gastrointestinal stroma at both mRNA and protein levels by RT-PCR, western blotting and immunohistochemistry. We found that 57% (16/28) of the tumor samples had a decreased PDCD5 expression at the mRNA level and 53% (35/66) of the samples were found to have decreased PDCD5 expression at the protein level, whereas PDCD5 was highly expressed in all adjacent normal gastrointestinal tissues at the mRNA or protein level. Moreover, decreased PDCD5 expression was significantly associated with clinicopathological characteristics including tumor size and mitosis. Our results suggest that PDCD5 expression plays a significant role in the malignant progression of human gastrointestinal stromal tumors and may be a key inhibitory factor.