BACKGROUND: We investigated the utility of gamma-glutamyl transferase-to-lymphocyte ratio (GLR) as a predictive indicator for postoperative survival in patients with hepatocellular carcinoma (HCC) across different time periods and developed a predictive model based on this. AIM: To evaluate the prognostic accuracy of GLR for overall survival (OS) in patients with HCC and its impact over time. METHODS: This study enrolled 301 patients with HCC treated with curative hepatectomy. Exclusion criteria included non-HCC hepatic malignancies, inadequate records, and prior cancer treatments. Baseline demographics, clinical features, and hematological parameters were recorded. Time-dependent receiver operating characteristic curve analysis was used to determine the optimal GLR threshold for survival prediction at 13 months. Statistical analyses included the Kaplan-Meier method, multivariate Cox regression, and the creation of a prognostic nomogram. RESULTS: Out of 301 patients, 293 were eligible for analysis, with a male predominance (84.6%). High preoperative GLR correlated with several adverse clinical features. Optimal cutoff values for GLR were significantly associated with stratification of 13-month OS. Multivariate analysis identified age, liver enzymes, postoperative transarterial chemoembolization, Child-Pugh grade, and inflammatory markers as independent predictors of OS. Notably, GLR had a significant impact on long-term postoperative OS, with its influence becoming more pronounced over time. CONCLUSION: GLR can serve as a potent prognostic tool for postoperative HCC management, particularly in predicting long-term outcomes.