Abstract： Objective To explore the value of serum Dickkopf-related protein 1 （DKK1）for the early diagnosis of esophageal cancer， and provide theoretical evidence for the diagnosis and treatment of esophageal cancer. Methods A total of 145 patients who were admitted to the Affiliated Hospital of Jiangnan University between October 2009 and April 2011 were included in this study and divided into four groups. There were 72 patients in the esophageal cancer group （54 males and 18 females with their median age of 60.4 years），13 patients in the precancerosis group （9 males and 4 females with their median age of 58.6 years），30 patients in the benign esophageal lesion group （23 males and 7 females with their median age of 56.4 years），and 30 healthy people in the volunteer group （19 males and 11 females with their median age of 58.6 years）. Serum DKK1 protein concentration was measured by enzyme linked immunosorbent assay （ELISA）. Receiver operating characteristics （ROC） curve was drawn to determine the cutoff level with optimal diagnostic accuracy. Results Serum DKK1 protein levels were significantly higher in the esophageal cancer group and precancerosis group than those in the volunteer group and benign esophageal lesion group ［（37.5±2.8） μg/L， （19.7±2.7） μg/L vs. （5.7±0.8） μg/L， （6.5±0.8） μg/L，t=47.391， P＜0.05］. There was no statistical difference in serum DKK1 protein level between the volunteer group and benign esophageal lesion group ［（6.5±0.8） μg/L vs. （5.7±0.8） μg/L， t=4.215，P=0.374］. When the level of serum DKK1 protein was 13.4 μg/L， the diagnostic sensitivity and specificity of esophageal cancer were 74.1% and 96.7%， respectively. Conclusion Overexpression of serum DKK1 protein could be related to the pathogenesis and progression of esophageal cancer. DKK1 protein may be a potential serologic biomarker for the early diagnosis of esophageal cancer.