Objectives To investigate the clinical value of the serum levels of CA125, CA72-4 and CYFRA21-1 in staging of esophageal cancer patients. Methods The serum levels of CA125, CA72-4 and CYFRA21-1 in 190 esophageal cancer patients and 79 healthy controls were measured by radioimmunoassay. The clinical pathological parameters in esophageal cancer patients were collected and analyzed. Results The serum levels of CYFRA21-1, CA72-4 and CA125 in esophageal cancer patients were increasing as their staging increased. The CYFRA21-1 levels in patients in stage of Ⅱa, Ⅲ, Ⅳ, and the lymph node positive group had statistical difference with the healthy control group (P<0.05). The CA125 levels in patients between stages of Ⅳ and Ⅰhad statistical difference（P﹤0.05）. The CA72-4 levels in patients in all stages had no statistical significant. Conclusion The serum CYFRA21-1 could be used to identify the early stage（stage 0 andⅠ）and advanced stage（stage ⅡB, Ⅲ and Ⅳ）. The serum CA125 might be used to identify the early stage and advanced stage, and the serum CA125 is obviously correlated with pT staging in esophageal cancer patients.