Golgi glycoprotein 73 (GP73) is a type II Golgi transmembrane protein and a potential novel marker for the diagnosis of primary hepatocellular carcinoma (PHC). However, its reliability as a serum marker for the diagnosis of PHC following transcatheter arterial chemoembolization (TACE) remains unknown. The aim of the present study was to evaluate the diagnostic value of serum GP73 levels in patients with PHC, to determine its diagnostic accuracy in patients with PHC following TACE. Reverse transcription-quantitative polymerase chain reaction analysis was used to measure GP73 expression in PHC and adjacent para-carcinomatous liver tissue in 40 patients with PHC, and 15 normal liver samples from benign hepatic tumors. The associations between GP73 expression levels with clinicopathological characteristics of the patients were also analyzed. Serum GP73 levels were detected by ELISA in 68 patients with PHC following TACE and 29 healthy individuals. The levels of serum GP73 were tested 2 days prior to intervention, and 7 and 30 days following TACE. GP73 mRNA expression levels in PHC were significantly higher than in the corresponding para-carcinomatous liver and normal liver samples. High expression levels of GP73 mRNA were associated with tumor size, vascular invasion and tumor differentiation, suggesting augmented tumor invasion and metastasis. The expression levels of serum GP73 were markedly higher in the patients with PHC compared with healthy individuals. Serum GP73 levels in the 68 patients with PHC were higher compared with the 29 normal controls [152.5 (76.4-284.5) compared with 49.3 (12.6-26.7) mu g/l], and the difference was statistically significant (P< 0.01). High levels of serum GP73 were associated with tumor differentiation. The levels of Barcelona clinic liver cancer stage A, B and C were 92.12 (38.9-135.2), 122.9 (55.2-178.5), and 162.55 (110.8-232.9) mu g/l, respectively (P< 0.05). The serum GP73 levels 7 days following TACE [99.2 (66.7-150.8)] were significantly lower than prior to TACE, and the difference was statistically significant (P< 0.05). In the group of 49 patients with serum alpha-fetoprotein (AFP) levels < 400 mu g/l, the serum GP73 levels were > 132 mu g/l. Serum GP73 levels may serve as a potential independent diagnostic marker for PHC, and the combined evaluation of serum GP73 and AFP may increase the diagnostic efficiency of PHC. Significant overexpression of GP73 mRNA was associated with aggressive PHC. However, further research is required to confirm the potential of GP73 as a diagnostic marker.