Gamma-glutamyltranspeptidase (gamma-GGT), an oxidative stress marker, is correlated with inflammation in the extracellular hepatic microenvironment. This study aimed to evaluate the prognostic value of serum gamma-GGT levels in patients with hepatocellular carcinoma (HCC) after hepatectomy. Three hundred and eight patients who underwent hepatic resection for HCC were included in the study. Preoperative serum gamma-GGT levels, as well as demographic, clinical, and pathologic data, were analyzed. The optimal cutoff value of gamma-GGT was 88 U/L. All patients were divided into gamma-GGT a parts per thousand currency signaEuro parts per thousand 88 U/L group (n = 146) and gamma-GGT > 88 U/L group (n = 162). The disease-free survival (DFS) and overall survival (OS) rates of patients in the gamma-GGT > 88 U/L group were poorer than those in gamma-GGT a parts per thousand currency signaEuro parts per thousand 88 U/L group. Preoperative serum gamma-GGT levels, associating with gender, HBsAg status, tumor size, capsulation, tumor number, and vascular invasion, was an independent prognostic predictor of disease-free survival [hazard ratio (HR) = 1.616; 95 % confidence interval (CI), 1.223-2.135; P = 0.001] and overall survival (HR = 2.043; 95 % CI, 1.509-2.766; P < 0.001). Furthermore, gamma-GGT was also associated with DFS and OS in small HCC (tumor size a parts per thousand currency sign5 cm) and alpha-fetoprotein (AFP) a parts per thousand currency signaEuro parts per thousand 200 ng/mL subgroup. In conclusion, gamma-GGT is a promising and reliable prognostic biomarker in HCC patients after hepatic resection, especially for patients with small HCC or AFP a parts per thousand currency signaEuro parts per thousand 200 ng/mL.