The aim of this study was to assess the value of malignant disease-associated DNA-binding protein 2(MAD2) in the diagnosis of liver cancer. The concentration of plasma MAD2 was determined in 27 patients with primary liver cancer, 14 patients with metastatic liver cancer and 12 healthy subjects by ELISA assay. The primary tumors of all the patients with metastatic liver cancer were located in the gastrointestinal tract, which had been radically resected and had no signs of local recurrence. The concentrations of plasma MAD2 in the patients with primary liver cancer, with metastatic liver cancer, and the healthy subjects were 30.56 +/- 11.38 micrograms/ml, 9.27 +/- 5.58 micrograms/ml and 8.43 +/- 5.62 micrograms/ml, respectively. The concentration of MAD2 in patients with primary liver cancer was significantly higher than that in the patients with metastatic liver cancer and healthy subjects (P < 0.001). There was no significant difference between the healthy subjects and the patients with metastatic liver cancer(P > 0.05). These results suggest that MAD2 may be an useful marker for the diagnosis of primary liver cancer.