Aim To evaluate the effect of Schlafen 1 (Slfn1) on the adhension of endothelial progenitor cells (EPC). Methods Ad-Slfn1, ShRNA-Slfn1, ShRNA-control and Ad-control were transfected into EPC respectively.Then EPC were plated on fibronectin-coated culture dishes, adherent cells were counted. The protein of Slfn1 and Cyclin D1 were examined by Western blot. EPC cell cycle was examined by flow cytometry analysis. Results On 48 h after transfected ShRNA-Slfn1, the expression of Slfn1 protein was decreased significantly compared to that in ShRNA-control group (P<0.05), the transfection of Ad-Slfn1 reversed these responses. Overexpression of Slfn1 suppressed the adhension of EPC; conversely, the silencing of Slfn1 using shRNA-Slfn1 increased the adhension of EPC. In addition, cell cycle was arrested G1 phase in Ad-Slfn1 group. Whereas the transfection of shRNA-Slfn1 reversed these responses. The expression of Cyclin D1 protein after transfection of shRNA-Slfn1 was increased clearly compared to that in ShRNA-control group (P<0.05), in contrast, overexpression of Slfn1 reversed these results. Cyclin D1 was involved in Slfn1-mediated EPC adhension. Conclusion Slfn1 reduced the adhension of EPC through Cyclin D1.