CXCR4 is the receptor of stromal cell-derived factor (SDF-1) and is expressed in many types of cancer cells. It also plays an important role in metastasis of malignant disease. In this study, we detected the expression of CXCR4 in 81 patients with myelodysplastic syndrome (MDS) by flow cytometry. We categorized MDS patients into the high-expression group and low-expression group according to CXCR4 mean florescence intensity ration thresholds. We showed that the high-expression group had a shorter overall survival time and shorter relapse-free survival time compared with those of the low-expression group (21.6 ± 1.9 vs. 46.0 ± 1.6 months, 17.0 ± 1.9 vs. 42.5 ± 2.1 months, respectively, P < 0.05), and Cox regression showed that CXCR4 was an independent prognostic factor. We conclude that the expression of CXCR4 is a useful prognostic factor for patients with MDS.