Although several studies have confirmed the clinical significance of the systemic inflammation markers in hepatocellular carcinoma (HCC), evaluating the clinical significance of each blood cell remains to be conducted. We aimed to evaluate the clinical importance of absolute counts of blood cells in the overall survival (OS) of patients with newly diagnosed HCC. We recruited patient cohorts from the prospective registry of newly diagnosed and previously untreated HCC at Samsung Medical Center, which included a training set of 6619 patients (2005-2013) and a validation set of 2084 patients (2014-2016). More than three-quarters of all patients had hepatitis B virus (HBV)-related HCC in both training and validation sets. The optimal cutoff values of the absolute counts of neutrophils, lymphocytes, monocytes, and platelets were 3917, 488, 1379, and 22,100, respectively, which correlated significantly with OS. The absolute blood cell counts categorized by each optimal cutoff value significantly correlated with liver function status determined by Child-Pugh class/albumin-bilirubin (ALBI) grade and the HCC burden determined by several staging systems/portal vein tumor thrombosis. Although the prognostic model based on these blood cells (ABC model) showed a lower prognostic ability than the Japan Integrated Staging or ALBI-T staging systems, it provided significant discrimination of survival in the subgroups of ALBI-T and showed the highest prognostic ability in the present study in the training and validation sets. Absolute counts of blood cells are independently associated with OS, though it is also significantly associated with liver function and tumor burden in newly diagnosed HCC.