Background: Cardiac valve calcification (CVC) is common in hemodialysis (HD) patients, and associated with cardiovascular and all-cause mortality. Once believed to be a passive process, it is now understood that the Wnt signaling pathway has a major role. The aim of the current study was to assess the relationship between circulating DKK-1, a negative regulator of the Wnt signaling pathway, and CVC, as well as carotid intimal-medial thickness (CIMT) in HD patients. Methods: We enrolled 74 consecutive adults on maintenance HD. Echocardiographic calcification of the mitral valve (MV) and aortic valve (AV) were detected according to Wilkins score (range 0-4), and the study of Tenenbaum et al. [Int J Cardiol. 2004 Mar; 94(1): 7-13] (range 0-4), respectively. CVC severity was calculated by a supposed score (range 0-8) that represents the sum of calcification grade of MV and AV. CVC severity was classified into absent (CVC score = 0), mild (CVC score = 1-2), moderate (CVC score = 3-4), and severe (CVC score ≥5). Demographic and biochemical data were collected in addition to serum DKK-1 levels and CIMT. Results: CVC was present in 67 patients (91.0%). There was a highly significant negative correlation between serum DKK-1 level and CVC score (r =-0.492; p ≤ 0.001), as well as CIMT (r =-0.611; p ≤ 0.001). Age and CIMT were independent determinants of CVC. Conclusions: CVC is almost present in all HD patients. DKK-1 seems to have a direct relation with CVC and CIMT in HD patients. Age is the strongest independent determinant of CVC.