〔Abstract〕 Objective To explore the value of golgi protein 73(GP73) and heat shock protein 90α(HSP90α) in the diagnosis of primary hepatic cancer(PHC) with low levels of alpha-fetoprotein(AFP). Methods ELISA was used to analyze the serum levels of GP73 and HSP90α in 50 cases of PHC with low levels of AFP, 30 cases of liver cirrhosis, 30 cases of hepatitis, 40 cases of healthy controls. Serum levels of GP73 and HSP90α among groups were compared. Results The serum levels and positive detection rates of GP73 and HSP90α were significantly higher in PHC group with low levels of AFP than those in the group of liver cirrhosis, hepatitis and healthy controls, and the difference was statistically significant(P<0.01). Serum levels of GP73 and HSP90α in PHC patients with low levels of AFP with lymph node metastasis and portal vein invasion were significantly higher than those in PHC patients without lymph node metastasis and portal vein invasion, and the difference was statistically significant(P<0.05). Sensitivity, specificity and accuracy rates in the diagnosis of PHC with low levels of AFP by GP73 alone were 78.0%, 77.0%, 77.3% respectively, while thoseviaHSP90α alone were 84.0%, 95.0% and 91.3% correspondingly. In the combined detection, the highest sensitivity of GP73 or HSP90α positive diagnosis was 94.0% and the highest specificity of GP73 and HSP90α positive diagnosis was 96.0%. Conclusion Both Serum levels of GP73 and HSP90α can be used as effective tumor biomarkers in the diagnosis of PHC with low levels of AFP and their combination significantly improves diagnostic accuracy with a higher sensitivity.