Objective To explore the clinical value of three serum tumor markers,Golgi protein 73( GP73),alpha- fetoprotein( AFP),and AFP- L3,in the diagnosis of liver cancer and recurrence monitoring after radio frequency ablation. Methods A total of 174 patients who visited our hospital from July 2012 to October 2013 were included in the study,consisting of 86 patients with newly diagnosed liver cancer,39 with liver cirrhosis,29 with hepatitis,and 20 healthy controls. Among the patients with newly diagnosed liver cancer,37 were followed up for three months after the radiofrequency ablation. Serum levels of GP73,AFP,and AFP- L3 were measured by ELISA,electrochemiluminescence,and affinity adsorption chromatography,respectively. Nonparametric tests were performed on the results of serum samples from the four groups which showed skewed distribution and were represented by median( quartile interval) [M( P25- P75) ]. Overall comparison was made by Kruskal- Wallis H test,and comparison between groups was made by Mann- Whitney U test. Pair- matching rank- sum test was performed using Wilcoxon Signed Ranks,and categorical data were analyzed by χ2test. Results The levels of GP73,AFP,and AFP- L3 in the liver cancer group were significantly higher than those in other groups( all P < 0. 05). The positive rates of GP73 and AFP- L3 in the liver cancer group were significantly higher than those in other groups( all P < 0. 05),and the positive rates of the two markers were significantly higher than that of AFP among patients with liver cancer( P < 0. 05). Thirty- seven patients with newly diagnosed liver cancer were reexamined three months after radiofrequency ablation,and the preoperational AFP- L3 level in the patients who had recurrence was significantly higher than that in the patients without recurrence( P < 0. 05). Conclusion Serum GP73,AFP,and AFP- L3 show great values in the diagnosis of liver cancer. AFP- L3 can be used as an indicator for the identification of benign or malignant liver disease and risk of recurrence after radiofrequency ablation.