Objective To investigate the diagnosis value of the serum levels of CA125, CA72-4 and CYFRA21-1 in patients with esophageal patients. Methods The serum levels of CA125, CA72-4 and CYFRA21-1 in 320 esophageal patients and 79 healthy controls were measured by radioimmunoassay. Results When the cut-off values of serum CYFRA21-1 was 1.8 ng/ml, the clinical significant is better than other cut-off. The levels of CYFRA21-1, CA-72-4 and CA125 in esophageal patients were significant higher than that of healthy controls (P＜0.01). The positive rate of CYFRA21-1, CA72-4 and CA125 in esophageal patients were 49.16%，30.89% and13.81% respectively. The positive rate of combination of CYFRA21-1 and CA72-4 was 65%, and that of combination of CYFRA21-1 and CA125 was 47.56%, that of combination of CA125 and CA72-4 was 31.00%. Conclusions The combined detection of CYFRA21-1 and CA72-4 are super than other two tumor markers.