The purpose of this study was to define the role of transcatheter arterial chemoembolization (TACE) in patients with a single large hepatocellular carcinoma (HCC) and define the patient groups benefiting from TACE. Treatment-naïve patients with preserved liver function who received TACE as the first-line treatment for single large (> 5 cm) HCC without macrovascular invasion and extrahepatic metastasis between 2007 and 2019 were retrospectively analyzed. Overall survival, progression-free survival, radiologic tumor response, complications, and predictors of survival were analyzed using multivariate analysis, and then a pretreatment risk-prediction model was created using the four predictive factors of tumor size, tumor type, ALBI grade, and ECOG performance status. Patients with scores of 0 (n = 54), 1–2 (n = 170), and 3–6 (n = 78) according to the model were classified as low-, intermediate-, and high-risk, respectively. The corresponding median OS values were 141, 55, and 28 months, respectively. The percentage of major complications increased as tumor size increased (4–21%). Asymptomatic, nodular HCC patients with a tumor size of 5–7 cm and ALBI grade 1 benefited the most from TACE. By contrast, the value of TACE in the treatment of single huge HCC (> 10 cm) with high complication rates remains unclear.