Introduction: This study evaluated the performance of the albumin-lymphocyte-globulin-C-reactive protein (CRP) (ALGC) index as a novel prognostic biomarker for hepatocellular carcinoma (HCC) after hepatectomy. Methods: Patients (n = 178) who underwent hepatectomy for HCC (July 2010–December 2021) were analyzed. The ALGC index was calculated as ([albumin × lymphocyte]/[CRP × globulin × 104]). Patients were divided into a low ALGC group (<1.82; n = 81) and a high ALGC group (≥1.82; n = 97). The association of the ALGC index with survival was assessed by univariate and multivariate analyses. Results: The median overall survival (OS) was 100 (range: 1–149) months with 1-, 3-, and 5-year OS rates of 91.6%, 81.2%, and 64.2%, respectively. In univariate analysis, ALGC index (<1.82), alpha-fetoprotein (≥25 ng/mL), tumor size (≥3.5 cm), microvascular invasion, and multiple tumors were associated with shorter OS. ALGC index (<1.82) (hazard ratio [95% confidence interval]) (2.48 [1.407–4.513]; p = 0.001) and multiple tumors (1.92 [1.070–3.356]; p = 0.029) were independent predictors of OS in multivariate analysis. Conclusion: ALGC index is a novel prognostic biomarker for HCC after hepatectomy. It may assist in treatment stratification and better management of patients with HCC.

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